Major Research Projects

This project investigates the mechanisms of protein homeostasis in oocytes, focusing on the balance between protein synthesis, folding, and degradation. Oocytes are unique in their ability to maintain cellular integrity and functionality over prolonged periods of dormancy. Understanding how protein homeostasis is regulated during oocyte development and maturation is crucial for identifying factors that impact oocyte quality and fertility.

By combining advanced proteomics, imaging, and functional assays, this study aims to uncover the molecular pathways that preserve proteome stability in oocytes, offering insights into age-related fertility decline and potential therapeutic interventions.

Can a Single Cell Learn?
Recent discoveries from labs worldwide suggest that not only neuronal networks, but even immune cells and single-cell organisms can “learn” from their environments. At the Fraticelli Lab, we are excited to explore how both healthy and malignant blood stem cells “learn” and retain these environmental “memories.”
To do this, we’ve created systems that record cellular experiences as multi-color reporter expressions, now being implemented in various cell lines, including mouse embryonic stem cells. By joining this project, the candidate will learn core research techniques, including blood and embryonic stem cell culture, transfection, cloning, fluorescence-activated cell sorting (FACS), and single-cell sequencing.
Working alongside lead researcher Andrea Polazzi, the candidate will receive close mentorship, with opportunities for significant skill-building in a cutting-edge research setting. This position also offers the possibility to stay on and take the project into new frontiers, exploring further aspects of cellular memory and its implications in both health and disease, such as cancer (immuno)therapy resistance.
If you’re passionate about the idea of cell “learning” and you’re eager to advance your expertise in stem cell research, we encourage you to apply. Join us in unraveling the mysteries of cellular memory!

We have discovered that somatic degeneration of human tRNA genes is a prevalent phenomenon that takes place in both healthy and cancer cells (1). Internal regions of tDNAs constitute hotspots of somatic mutagenesis whose intensity is directly linked to the transcriptional activity of each gene.
The mutational load at tDNAs is not found at other genes transcribed by Pol III, and accumulates in tDNAs at rates up to 10-fold higher than in protein-coding genes. Somatic mutations at tDNAs happen in both healthy and cancer cells, accumulate with age, and are capable of generating mutant chimeric tRNAs that decrease the quality of the human proteome through specific and ubiquitous amino acid substitutions.
We have begun to generate cell lines that express the mutant chimeric tRNAs that we most often detect in human tumors. We are seeking a motivated Ph.D. student to push this project forward. Interest in cell culture and in studying cancer and aging from the perspective of fundamental cell biology are needed.

Cells are constantly exposed to mechanical forces from both their extracellular environment and internal processes. Their ability to sense and respond to these forces is essential for critical cellular events, which is achieved by a complex machinery of mechanosensitive structures that operate with exquisite precision at the molecular level. Disruptions in these processes can lead to multiple diseases like cancer, fibrosis, and immune disorders. Despite recent advances in force measurement tools, visualizing the effects of these forces at the molecular level and in living cells remains challenging.

Our laboratory, in collaboration with the group of Pere Roca-Cusachs at IBEC, has recently developed an innovative cell stretching system compatible with super-resolution fluorescence microscopy and other advanced imaging techniques. This state-of-the-art device allows to exert mechanical stimulation in living cells in a controlled manner and visualize how cells adapt and respond to the forces in real time, offering unprecedented potential to push the boundaries of cell mechanobiology. In particular, the candidate will use the devices to stretch living cells in combination with Stimulated Emission Depletion STED super-resolution microscopy and other imaging techniques. The focus will be on studying mechanosensitive membrane proteins that form nanoscopic assemblies and initiate protein interaction cascades in response to mechanical stimuli.

Candidates with a background in physics, chemistry or biology are encouraged to apply. The student will work in an interdisciplinary group and will gain wet lab skills, hands-on experience in cell culture, fluorescence labelling of proteins, advanced super-resolution fluorescence microscopy techniques, image analysis and in writing and presenting the research results to a multidisciplinary audience.

Innate immune cells, such as dendritic cells, macrophages and neutrophils, control immunity and the health of organs. Therefore, they are present in virtually all body tissues. We aim to understand how innate immune cells can persist in and adapt to different milieus of tissues, such as limited nutrient concentrations and other variables. In that regard, our main research line focuses on revealing the adjustments of the cellular metabolism by dendritic cells, macrophages and neutrophils to changing environments in health, cancer and obesity-related pathologies. Our ultimate goal is to identify the requirements or vulnerabilities of innate immune cells to improve or target their dysfunctions during those non-infectious diseases by “innate immunotherapies”. The detailed Master’s project is flexible and will be designed together with the successful candidate based on her/his interests within our research lines.
We are looking for a motivated Master candidate to investigate the homeostatic and immunogenic behaviour of dendritic cells, macrophages and/or neutrophils under different environmental or metabolic conditions in vivo and in vitro. This will include the variation of metabolites, temperature, pH, genetic interference with cellular metabolism and/or other alterations of the surroundings. Our main model systems are laboratory mice and we will provide training in harvesting and processing their organs for research. Moreover, the candidate will perform analyses of the functions of innate immune cells, such as migration, phagocytosis, expression of functional markers and cytokine production. Subsequent experimental techniques will include the isolation or differentiation of innate immune cells for primary cell culture, co-culture assays, flow cytometry, gene expression analysis, ELISA, fluorescence microscopy and metabolic assays. Additionally, we offer teaching of experimental design, data analysis, visualisation and interpretation as well as help with the oral presentation of the candidate’s research results.

Complex systems unravel an intriguing interconection of several variables and determinants. Their complexity requires a huge effort sometimes attacked using Big Data artillery. A completely different approach tries first to understand the small scale dynamics for later extrapolate it to the large scale with the appropriate tools. This latter methodology has been employed in Particle Physics with extraordinary success. The attempt of this project is to proof whether a similar approach can be devised for urgent eco-social problems such as the climate and its climate change dynamics, neurogenesis and carcinogenesis. The expected outcome is a set of in-silico simulations of several of these scenarios with the attempt to provide a digital-twin for further investigations.

The overall goal of the project is to study the implications of the abnormal lipid accumulation in lysosomal storage disorder lipidoses, on membrane biomechanical properties and how this correlates with endocytosis and vesicular trafficking, in order to set the basis improved treatments capable of reverting the lipid accumulation and associated biomechanical/cell biology effects. The student will be involved in the design and building of supported lipid membranes, and their characterization using force spectroscopy (indentation and tube-pulling) based on AFM. The student will be trained on lipid vesicles and membranes preparation, surfaces functionalization, and to work with SPMs techniques. He/she will also learn on bibliographic search, data treatment and presentation (written and oral) of the results. The student will incorporate to the Nanoprobes & Nonsnitches research group and will actively participate in the meetings and discussions. He/she will acquire basic competences related to the experimental work in a multidisciplinary lab on nanobiotechnology.

While the visualization of quantum dynamics has seen significant development and has established itself as an industry, the realm of sonification, the process of translating quantum dynamics into sounds, remains relatively unexplored. This involves the generation of sounds, either digitally (via classical or quantum computer) or analogically (using musical instruments) derived from simulations or laboratory data across diverse quantum systems.

The Master’s project is profoundly interdisciplinary, encompassing: a) the fundamentals of quantum mechanics, with a focus on the theory of individual quantum trajectories, quantum many-body physics, and quantum many-body dynamics; b) diverse approaches to mapping quantum data to sound; c) the utilization of specialized audio programs (such as SuperCollider) to translate data into various sound parameters; and d) foundational knowledge in acoustics, music theory, and data sonification.

The ideal candidate will possess a solid background in quantum physics and computer simulations. A basic understanding of acoustics and music theory is required, coupled with an openness to experimental music research. While experience in audio synthesis, coding (with various audio programming environments), and algorithmic composition is highly advantageous, it is not mandatory.

This project focuses on the development of single-cell coatings using extracellular matrix (ECM)-derived biomaterials to create a bioactive coating that protects neural cells and boosts their functionality, particularly during and after the bioprinting process. Single-cell coatings provide a micro- or nanoscale protective layer that enhances the cellular microenvironment, supporting essential cell functions and promoting cell interactions. Building on promising initial experiments with ECM-coated neural cells, this project will optimize single-cell coatings using various biomaterials and bioactive molecules. The process will include specific ECM preparation steps to create a cell-friendly environment. This single-cell coating protocol, designed to enhance cell survival and functionality, will then be evaluated for its application in 3D bioprinting of in vitro spinal cord models. By establishing a reliable method for single-cell coating, we aim to create a bioactive microenvironment that promotes specific cellular behaviors and preserves viability, supporting advances in bioprinting and cell therapy research.

The student will gain hands-on experience with essential techniques, including cell culture, biomaterials processing, bioprinting and advanced microscopic imaging. The candidate will also develop key skills in literature review, data analysis, and result presentation (both written and oral). Engaging within a motivated and multidisciplinary research group, the candidate will build independence while thriving in a collaborative environment.

Decellularized extracellular matrix (ECM)-based bioinks are valued for their ability to provide complex physical, chemical, biological, and mechanical cues, which are difficult to replicate using simpler biomaterials. However, the low viscosity and poor mechanical stability of ECM bioinks make 3D printing challenging, often requiring combination with other biomaterials to achieve structural integrity.
This project aims to develop a specialized support bath that enables 3D printing of low-viscosity ECM-based bioinks specifically designed to create a patch for cardiac tissue engineering. The support bath will enhance printability, stabilize constructs, and support ECM fibrillation by using macromolecular crowders.

The project will be divided into three main objectives:

Support Bath Development: Design and optimize a support bath with rheological properties suited to stabilize the 3D printing of low-viscosity ECM bioinks.

Optimization of Crowder and Salt Ratios: Determine the ideal concentrations of macromolecular crowders and salts to promote ECM fibrillation thereby enhancing post-print stability and mechanical strength for cardiac patch applications.

Scaffold Printing and Evaluation: Print and assess various scaffold designs using the optimized support bath. Evaluate structural and functional properties, including fiber diameter, collagen alignment, and mechanical characteristics, to determine suitability for cardiac tissue engineering.

The student will gain practical experience in 3D bioprinting, biomaterial development, rheological and mechanical analysis of biomaterials, decellularization of cardiac ECM, and cardiac tissue engineering, with a focus on designing a scaffold to support cardiac repair.

Dierssen Lab:
Our research is centered on understanding cognition and behavior and their perturbation in intellectual disability. Our main question is: what are the changes in brain cell architecture and connectivity that disrupt brain function in cognitive disorders, and specifically in Down syndrome? In other words, what is the multi-scale link from molecular alterations to impaired cognition and behavior? To these aims we focus on quantitative neuroscience at multiple levels (behavior, 3D imaging, genomic data) of many variables of the system (longitudinal behavioral analysis, population-based analysis in neuronal networks, gene expression patterns) allowing to acquire a system-level understanding of brain disorders and to accelerate pre-clinical drug evaluation. This is leading to the discovery of new mechanisms, and identified key genes for brain pathology in intellectual disability and Alzheimer’s disease.

Al Jord Lab:
Our group is on a mission to uncover mechanisms that cells deploy to functionally remodel their organelles in health & disease. One of our key research areas focuses on the relation between biophysical forces and essential nuclear organelles known as biomolecular condensates, which are key in processing genetic information. Our goal is to understand how cytoskeletal forces mechanically impact nuclear dynamics across scales, from condensate remodeling down to RNA-processing regulation, and how this biophysical relation influences cell division and specialization. By understanding these processes, we can potentially develop new ways to treat serious diseases associated with changes in cell mechanics, like cancer and premature aging.

Project description:

The Dierssen and the Al Jord labs are collaborating in a quest to understand how Down Syndrome (DS) impacts multiciliated cells, which are vital for human brain, respiratory, and reproductive health. We suspect that they are dysfunctional in DS, and that this may contribute to multisystemic disease aggravation.

Using an interdisciplinary methodology, the student will explore how brain multiciliated cells in a DS model develop both in vivo and in vitro. A key research focus will be to document, with state-of-the-art tools, the obscure mechanical relation between the cytoskeleton and nuclear biomolecular condensates in control and DS mouse brain multiciliated cells. Our toolbox includes techniques like brain dissections, neural stem cell cultures, protein multiplexing, advanced live and super-resolution imaging, spatial transcriptomics, and force measurement and modulation assays.

Objectives:

1. Investigate the role of multiciliated cells in Down syndrome: Characterize the structure and function of multiciliated cells in DS models, aiming to understand how DS affects these cells in the brain ventricles and contributes to neurodevelopmental phenotypes.

2. Elucidate the cytoskeletal and nuclear dynamics in DS multiciliated cells: Explore the mechanical relationship between the cytoskeleton and nuclear biomolecular condensates in multiciliated cells of DS models using advanced imaging and molecular techniques, to uncover potential pathways of dysfunction specific to DS.

We are looking for a student with a background in Neurobiology, Cell Biology, Molecular Biology, or Biophysics, who is interested and excited about the mysteries of DS, aging, cytoskeleton, biomolecular condensates, and mechanobiology as we are.

The scientific aspects of the project will be supervised by Dr. Dierssen and Dr. Al Jord in weekly meetings and day-by-day discussion along with a lab researchers. This will allow to quickly incorporate technical and training aspects necessary for the proper development of the project. The CRG and the Parc de Recerca de Barcelona offer a rich scientific environment with experts in the field of biomedicine. Moreover, the CRG has a training series (“Courses@CRG”).

Solar energy is a particularly attractive and widely distributed energy source, making solar fuels an attractive option for future energy generation. The conversion of sunlight into chemical energy offers a sustainable alternative to fossil fuels, contributing significantly to the mitigation of climate change and the enhancement of energy security.

To achieve this, the main goals of the project will be focused on,
a) the development of efficient and robust semiconductors
b) the development of molecular redox catalysts for oxidation of water and reduction of CO2
c) the anchoring of the catalysts into semiconductors and
d) the construction of a solar fuel generating device.

The student will be introduced into the cross disciplines of materials science and molecular chemistry and the synergistic benefits this brings to build devices useful for technological applications.

Slc13a5 deficiency disorder presents with epilepsy in the first week of life that persists into adulthood and causes developmental delay, and is caused by loss-of-function mutations in the plasma membrane sodium/citrate cotransporter. However, little is known about this rare genetic disorder, and current treatment is limited to antiepileptic drugs with variable success in seizure management and little to no improvement of intellectual disability.
Our aim is to investigate whether astrocytes play a role in Slc13a5 deficiency, as these brain cells are understudied but express high levels of the transporter, and to explore astrocytes as targets for better treatments. The first aim of this MMRES Master project is to create an in vitro model of the disease, including its epileptic phenotype, using cells from patients and isogenic controls, to test whether disease astrocytes alone cause defects in normal neurons. Further aims are to characterize which soluble factors from astrocytes affect neurons and use our in vitro model to test the efficacy of drugs in improving cell metabolism and minimizing neuronal dysfunction. The techniques used will involve cell culture and differentiation into astrocytes, neurons and brain organoids, infection of CRISPR constructs and biosensors via adeno-associated viruses, and imaging via confocal and two-photon microscopy to monitor pathological morphology and neuronal/astrocytic cell activity.
The Nanoprobes & Nanoswitches lab, that hosts the supervisor of this project, has expertise in a wide range of techniques including molecular and cell biology, chemical synthesis and imaging experiments in a variety of models, such as mouse, zebrafish, xenopus, cell lines and culture of patient-derived cells. We are looking for a student excited to take up this project on Slc13a5 deficiency and advance diagnosis and treatment of this currently incurable disease.

The overarching goal of the NMSB lab at ICFO is to devise optogenetic methods for studying and manipulating the brain. We have recently re-engineered the connectome of a small model organism using photons as synaptic transmitters (PhAST [1]). Leveraging presynaptic expression of light-emitting enzyme (luciferases) and postsynaptic light sensors (channelrhodopsins), we re-connected broken neuronal circuits and wired together naturally unconnected neurons to establish synthetic neuronal circuits. In this current project, we aim to use PhAST to overcome spatial discontinuities (e.g. axotomies) in a model for spinal chord injury. Re-innervation in spinal chord injury suffers from several challenges that include axon regrowth, reconnection of the severed ends and correct matching of the neuronal endings in a fasciculated nerve [2]. To overcome these challenges, we will use luciferases and channelrhodopsins that are co-expressed in a single neuron within a nerve cell bundle of Caenorhabditis elegans. To follow the successful, functional reconnection, we will use indicators of neuronal activity and read-out signal propagation across the lesion, in presence and absence of PhAST. During the course of the master thesis, the student will learn how to genetically manipulate C. elegans, use microfluidic devices for animal immobilization, imaging and mechanical stimulation. At the end of the thesis, we expect to investigate how photons can be used to overcome transmission defects in C elegans setting the stage for work in an mammalian animal model of spinal chord injury.

[1] Porta-de-la-Riva, Nature Methods, 2023; Neurophotonics, 2024
[2] Peterson, Front Neurol, 2021

RF resonators have been used in laboratories sensing different biological samples. Our goal is to push this technology further by completing the design of a small device, able to work as benchtop apparatus and providing reliable quantification of different compounds in biological solutions. Our objectives are to assess the reliability of the measurement method with easy samples (water+ethanol), try trinary solutions and finally move to synthetic urine with some compounds that could be used as biomarkers of cancer. At the end, you’ll have accumulated knowledge of a promising sensing technique, ways of producing a prototype, use instrumentation devices with biological samples and some electronics.

We are an interdisciplinary group studying intracellular membrane morphology and dynamics, with a special focus on understanding the secretory pathway. We combine advanced microscopy techniques (single-molecule fluorescence and super-resolution nanoscopy), molecular and cell biology tools, with theoretical biophysics approaches to tackle highly controversial or still mysterious fundamental topics in cell biology with a clear pathophysiological relevance.

This MSc project will verse on understanding intracellular trafficking mechanisms, in particular that of the formation of transport carriers at the endoplasmic reticulum (ER) for secretion outside of the cell. The mechanisms for how different challenging cargo proteins, such as collagens, are exported out of the ER are still incompletely understood. The study of protein export from the ER using conventional microscopy tools has provided important but still limited information about this process, mainly due to the highly dynamic nature and intricate morphology of this organelle. As a result, a clear understanding of the how proteins are sorted into ER exit sites and exported out of the ER is still lacking.

The role of the MSc student will be to perform a set of innovative assays that combine different state-of-the-are molecular and cell biological techniques, such as the use of retention using selective hooks (RUSH)-system, with state-of-the-art microscopy tools, such as single-particle tracking photoactivatable localization microscopy (sptPALM), a toll that allows us to monitor the dynamics of individual cargo molecules with a spatiotemporal resolution of ~10 ms and ~10 nm. The data obtained will be analyzed using advanced quantitative imaging deep-learning-based tools to finally cast light on the mechanisms of secretory protein export out of the ER.

The design and synthesis of novel hybrid electrodes based on nanomaterials provides synergic paths to improved performance. This master would include the synthesis of hybrid electroactive materials based on conducting carbon and redox active inorganic species. The full study of these materials will include basic characterization (SEM/TEM, FTIR, BET, XPS…) and emphasis on electrochemical characterization (CV, GCD) leading to the testing of energy storage performance.

Depression affects millions of people worldwide and mental health disorders are on a rise. Despite this, most drugs used to treat clinical depression are decades old and have low success rates and slow onset, which is one of the main complaints of patients. To address this, the veterinary anesthetic and recreational drug ketamine was recently repurposed for treatment-resistant depression, showing a rapid onset of antidepressant action of hours or days compared to slower onset of classical antidepressants. However, ketamine pharmacology is complex, and it binds many receptors beyond NMDA, including the BDNF receptor TrkB, which is expressed on both neurons and astrocytes, and governs synaptic plasticity.
The goal of this project is to explore whether and how ketamine acts on astrocytes and affects neuroplasticity via TrkB. The student will work on astrocyte-neuron primary co-cultures and adeno-associated viral delivery of biosensors of intracellular signaling and cytoskeletal mobility, to test whether ketamine recruits astrocytes driving morphological rearrangements and supporting synaptic plasticity. Results from wild type cultures will be compared to cultures lacking astrocytic TrkB to evaluate the specific contribution of astrocytes to neurotrophic factor signaling. Other techniques used for this project will be molecular biology, CRISPR knockout, immunohistochemistry and confocal imaging.
The Nanoprobes & Nanoswitches lab, that hosts the supervisor of this project, has expertise in a wide range of techniques including molecular and cell biology, chemical synthesis and imaging experiments in a variety of models, such as mouse, zebrafish, xenopus, cell lines and primary cultures.
We are looking for a student excited to take up this basic neuroscience project to advance our understanding of how ketamine exerts its antidepressant effects and potentially lead to improved therapies.

My research focuses on Cancer Engineering within Bioengineering for emergent and advanced therapies, with a particular emphasis on developmental (pediatric) cancers, including neuroblastoma (NB), osteosarcoma (OS), and Ewing’s sarcoma (ES). By developing 3D tissue-engineered tumor models that closely replicate the tumor microenvironment, I aim to capture critical aspects of human tumor behavior in vitro, such as therapeutic targeting and efficacy. These advanced models function as predictive, high-throughput platforms that support the development of nanocarrier-based, patient-specific therapies. My work bridges fundamental cancer research and translational applications, accelerating the pathway toward personalized treatments uniquely tailored to the biology of pediatric cancers.

This MMRES project focuses on developing advanced tumor-on-a-chip platforms to study metastasis in NB, OS and ES. Building on previous work, we will use the validated “bone marrow-on-a-chip” model to investigate cancer cell interactions with bone marrow components and tumor spreading mechanisms. Additionally, we aim to fabricate and validate a “lung-on-a-chip” system to study the metastatic process to the lung microenvironment.

The objectives are:
1. Adapt the bone marrow model for studying OS and ES metastasis.
2. Design and fabricate a novel lung-on-a-chip system for investigating developmental tumors spread to the lung.
3. Compare metastatic mechanisms across these three cancers to identify common and unique pathways.
The student will gain hands-on experience in microfluidics, biomaterials formulation, and tissue-engineering techniques. They will also learn advanced imaging, molecular biology methods and data analysis for studying tumor progression. The project provides interdisciplinary training in bioengineering, oncology, and translational cancer research, preparing the student for future academic or industrial research roles.

Aneuploidy, which is the major cause of miscarriages in humans, is pervasive in early human embryos but is robustly dampened during development to lead to healthy births. A mechanistic understanding of the identification and elimination of aneuploid cells remains poorly understood. We use Drosophila to characterize whether this process relies on cell interactions and to identify the underlying molecular mechanisms. This project will certainly have implications in understanding the major cause of miscarriages in humans.

The group’s objective is to enhance our quantitative understanding of a phenomenon, which is ubiquitous in the natural world: biological evolution. Quantitative models of evolution have to consist of (at least) two components: variation through random mutation and natural selection. To model the first component, we must examine how random mutations in biological sequences give rise to higher-order molecular and phenotypic changes, which selection then acts on. As an example, let us consider the effects of random RNA sequence mutations on folded RNA secondary structures: we can start with one specific sequence and analyse, how its secondary structure changes after one specific mutation. However, sequences change during evolutionary processes, and so one important challenge is to gain a more general quantitative overview that describes the effects of an arbitrary mutation on an arbitrary sequence. This can be achieved with concepts from the fields of genotype-phenotype (GP) maps and fitness landscapes. These concepts are sufficiently abstract that they are not only useful for the example of RNA, but also for other molecular structures and for phenotypic changes beyond the molecular scale. With this approach, we can gain a better quantitative understanding of variation, and investigate the interplay between variation and selection in evolutionary processes.
This will be a computational/theoretical project, and thus offers an opportunity for students with a highly quantitative background (physics, mathematics etc.) and some programming experience (ideally Python) to apply their skills to exciting biological questions. The student will develop their skills in planning, writing and analysing computer simulations, and gain expertise on the topics of genotype-phenotype maps, fitness landscapes and evolutionary processes.

The aim of the project is to recognize and identify defects in Materials for Energy transformations. To this end we will employ Artificial Intelligence strategies coupled to the most advanced simulation techniques and verify the models we construct against experimentally available data. The aim of the project is to deliver a tool for the identification of structural defects and impurities.

The motivation of this Master project is the need to face the global challenge of achieving a renewable, widespread, safe and inexpensive energy supply to contribute to our society ecological transition in order to attain a more sustainable future. The energy of the Sun is the most promising energy source since it fulfils the above-mentioned requirements. Hence, within this project, the Master student will construct novel bio-inspired chromophore-protein assemblies (de novo designed proteins) capable of absorbing solar energy and converting it into a stable separation of charges. Crucial to this project is the implementation of the quantum design principles of photosynthesis, that is delocalized excited states with charge-transfer character, vibration-assisted electronic coherence among the electronic states involved in energy and electron transfer processes, and the presence of a smart protein matrix to control the energy landscape of the system. The methods to be applied to understand the properties of the assemblies will be mainly spectroscopic techniques, both steady-state (absorption, fluorescence, linear and circular dichroism, Raman, and Stark) and time-resolved (ultrafast transient absorption). More specifically, the investigated assemblies´ properties will be: electronic and vibrational energy levels, protein folding and thermal stability, chromophore orientation within the protein, excitonic interactions, energy and electron transfer dynamics and the role of quantum coherence in those dynamic processes. During the project, the student will acquire wet lab skills (handling of chromophores and proteins), and technical skills on the above-mentioned spectroscopic techniques. In addition, the student will enhance her/his writing and oral skills with the composition of reports and the presentation of her/his research to an international community, together with the participation in group discussions to support the project progress. Knowledge in physics, chemistry or materials science will be beneficial to fulfil the project objectives.

The goal of this project is to engineer motile synthetic cells capable of movement through the dynamic reshaping of their membranes, driven by enzyme-powered nanomotors. This type of motion is inspired by natural cellular behaviors, where cells use appendages or generate protrusions to navigate their environment for feeding, communication, tissue remodeling, or pathological processes such as cancer progression.
Our aim is to integrate force generation at the nanomotor-membrane contact points, self-organized nanomotor clustering, and membrane morphing into a feedback loop that regulates the motion of this active system. The nanomotors transform a chemical fuel into forces at the contact points with the membrane and deform it during their motion. Thus, the deformation and propulsion become coupled, similar to the motion of cells mediated by the cytoskeleton.
Role of the Student:
The student will focus on functionalizing synthetic cells with nanomotors. These nanomotors will be either encapsulated within the lumen or anchored to the external leaflet of the membrane. The project will involve studying the self-organization of nanomotors on the membrane, with the potential to uncover emergent collective behaviors that enhance propulsion.
In subsequent steps, the student will investigate the ability of these synthetic cells to “crawl” along extracellular matrix (ECM) surrogates. The membranes will be equipped with receptor molecules designed to mimic integrin-mediated attachment, binding to specific ligands on the matrix. By engineering membranes that support lateral receptor organization influenced by curvature, we aim to couple receptor binding and selectivity with membrane deformation and nanomotor activity.
This work will provide insights into the principles of motion in synthetic cells, paving the way for applications in biomimetic systems and active matter research.

An important part of the group’s work focuses on the mechanisms of signal integration by the p38 MAPK pathway and its implication in physiological and pathological processes. There is evidence supporting that p38a plays important roles in the regulation of normal tissue homeostasis but can be hijacked during tumorigenesis, facilitating tumor formation and therapy resistance at different levels.

Our work combines biochemical and molecular biology approaches with experiments in cultured cells and studies using mouse models and chemical tools.

The group has the ambition to identify new therapeutic opportunities based on the modulation of p38 MAPK-regulated mechanisms that control cancer cell fitness and the response to chemotherapy. We are also performing screenings to find actionable targets that can be used to boost current cancer therapies as well as to design new targeted therapies for particular cancer types.

The student will work under daily supervision of an experience group member who will teach the student the techniques and experimental design, as well as how to analyze and interpretate the results, and to write the lab notebook.

Rapid growth and success of personalized medicine will depend on the development of new technologies that target individual disease mechanisms. Often, specific diseases require the targeted activity modulation of a subset of neurons within a neuronal circuit, without affecting neighbouring cells. Neuromodulation using light, through expression of light-gated ion channels (e.g. channelrhodopsin) in neurons bears tremendous promise due to the unprecedented spatiotemporal control over which light can be delivered. In humans, however, this requires surgical implantation of a light-delivery device close to the target cells – a procedure that largely limits the transition of optical neuromodulation techniques from the bench to the bedside. In addition, channelrhodopsin expression in neurons may cause unwanted side effects, and are characterized by poor photophysics (absorbance, photocurrents, ion selectivity).
In this project aim to combine endogenous light-delivery through targeted expression of luciferases [1] and photopharmacology [2], which leverages light control over endogenous neurotransmitter receptors. To demonstrate the feasibility of this approach, the student will express luciferases in one cell and target endogenous neurotransmitter receptors in another. He/she will create co-cultures and incubate them with molecular photoswitchable compounds that are color-matched to the emitted light, and which, once activated, bind to and trigger the specific receptor. Importantly, this approach leverages the expertise of both teams in optogenetics and photopharmacology and will overcome challenges in light delivery to activate endogenous receptors to open the door to new treatment options in applied medicine. 
This project will be carried out at ICFO in the NMSB lab in collaboration with IBEC under co-supervision of Pau Gorostiza and Galyna Malieieva from the Nanoprobes and Nanoswitches group.

[1] Porta-de-la-Riva, Nature Methods, 2023; Neurophotonics, 2024
[2] Castagna, FEBS3+, 2022

We are ultimately interested in deciphering the mechanisms that control cell cycle progression with a special focus on the G1/S transition. In metazoans, inactivation of the Retinoblastoma protein (pRB) leads to unregulated cell cycle progression promoting uncontrolled cell growth, genomic instability and aneuploidy, hallmarks of tumor progression. pRB tumor suppressor activity is achieved through binding and regulating the E2F family of transcription factors. It is well known that a tumor process is very complex, accumulating numerous secondary mutations that aim to eliminate the brakes to the proliferative process. Even though many individual regulators of the pRB-E2F complex are known, an integrative view of all the regulatory events controlling the G1/S transition is required to anticipate putative interventions able to block proliferative processes.
Using reverse genetics and by introducing a set of short-lived fluorescent markers in a KO library, we have recently isolated potential genes involved in the G1/S transition. Among them, we have found some components of the TOR pathway, members of the ubiquitin-mediated protein degradation and several chromatin remodelers. The Master BIST candidate will characterize (some of) these potential regulators, measuring their direct effect on the regulation of the G1/S transcriptional wave and which is their specific impact on cell cycle progression. The experimental approach will include genome-wide approximations (RNAseq, ChIPseq, proteomics) and confocal microscopy (using a cell cycle reporter that we have also recently developed in the laboratory, Murciano-Julia et al, PLoS Biol, 2024).
Required student background: A high motivation towards a scientific career in projects related to basic research. Also, a solid background in Genetics, Cell Biology and Molecular Biology is a plus to carry out this project. To analyze the results (i.e., ultrasequencing or targeted proteomics), knowledge of bioinformatics will be beneficial for the candidate.

In the mammalian intestine, different cell types display distinct gene expression programs not only according to their function and position within the tissue but also in a time-dependent manner. One of the main contributors to the temporal and spatial orchestration of intestinal homeostasis is the circadian clock. The circadian clock keeps the intestine synchronized with the rest of the organs and tissues in the body and with the cyclic 24-hour environment. We are progressively learning how different signalling pathways coexist and impact time in this complex tissue, but still very little is known about the role of mechanics, whose signalling is of much importance, given the intestine is subjected to cyclic mechanical stress.

The student who choses this project will study the effect of mechanical signalling on the small intestine epithelium, focusing on how mechanotransduction impacts the circadian rhythms of individual cells. They will carry out this project using a multidisciplinary approach that includes cell culture (2D and 3D small intestine mouse organoids), microfabrication, microfluidics, confocal microscopy, and computational analysis, all of them technologies well established in the host lab. The main aim of this project is to help us understand if intestinal clocks are subjected not only to endocrine but also to mechanical regulation, and how this new signalling pathway differentially impacts the program of the different intestinal cell types.

Alzheimer’s Disease (AD) affects around 50 million people worldwide, and despite tremendous efforts to find a treatment, little success has been achieved. This highlights the need for a better understanding of the disease’s mechanisms. This project aims to address this need by investigating the early stages of neuronal degeneration in AD, particularly in the axon, using a live-cell imaging approach.

Due to their morphology, neurons are particularly susceptible to traffic jams or other mechanical perturbations in their protrusions. Tau, one of the key players in AD, is a microtubule-associated protein that transiently interacts with microtubules in healthy axons. These microtubules are used by neurons to transport important cargo to and from synapses. In AD, this protein transitions into solid aggregates. However, how tau’s initial solid transition affects axonal transport or overall axonal integrity is still unclear.

Briefly, we will use a seeding strategy to trigger tau’s solid transition in axons and study the immediate consequences of this transition for axonal transport in live neurons. Neurons derived from human iPSCs, as well as mouse primary neurons, will be used in this study.

We are looking for a motivated and curious student, ideally with a background in Cell Biology, Biochemistry, or Biomedicine. The student will receive training to generate tau seeds from recombinant tau. He/she will learn various fluorescence-based techniques to analyze tau solid transitions and axonal transport defects, such as fluorescence recovery after photobleaching (FRAP). The student will also gain experience working with human iPSCs and differentiating them into mature neurons, as well as dissecting primary neurons and plating them in microfluidic devices. Additionally, he/she will learn basic molecular biology techniques such as Western blot, immunostaining, and semi-automatic data quantification and analysis.

Understanding the brain is one of the greatest scientific challenges of our times, requiring cutting-edge tools to unravel its complexity. Two-photon (2P) microscopy is transforming neuroscience by enabling us to image neurons in action and manipulate their activity with unprecedented precision.
However, traditional 2P microscopy has a key limitation: it’s performed in head-fixed animals, preventing the study of natural, free behavior. To overcome this, few groups have started the ‘miniaturised microscope revolution’ and developed portable 2P microscopes to image neuronal activity in freely moving mice. Our group has developed 2P-FENDO, the first portable fiberscope that enable not only imaging but also 2P optogenetic stimulation (Accanto et al., Neuron 2023).

While groundbreaking, 2P-FENDO has limitations: a small field of view (~250 µm), giving access to fewer than 50 neurons, and suboptimal signal quality due to distortions in the laser pulse through the fiber. This master’s project aims to overcome these hurdles and deliver a next-generation 2P-FENDO. Using optical engineering, we will (1) design an advanced micro-optical system for improved imaging and (2) develop new laser pulse compression techniques to boost signal quality and maximize fluorescence detection.

As part of the project, the student will gain hands-on experience with powerful infrared lasers, optical design, and nonlinear optics. The student will also be trained in the use of 2P-FENDO and will be implicated in biological experiments to study the brain. This is an opportunity to push the boundaries of neuroscience technology and help decode how the brain drives behavior.

Understanding the brain is one of the greatest scientific challenges of our times, requiring cutting-edge tools to unravel its complexity. Two-photon (2P) microscopy is transforming neuroscience by enabling us to image neurons in action and manipulate their activity with unprecedented precision.
Precise optogenetic manipulation of ensemble of neurons with single cell resolution can be obtained by using spatial light modulators (SLMs) and computer-generated holography (Accanto et al., Optica 2018, Emiliani et al, Nature Reviews Methods Primers, 2022).

However, when used together with ultrafast laser pulses, characterized by a large spectral bandwidth, SLMs can only be used to generate excitation spots on a small field of view (FOV). Today, state of the art 2P microscopes are capable of imaging neuronal activity on a 5 mm FOV with individual neuron resolution, allowing the observation of 1000s of neurons at the same time. The FOV for 2P optogenetic photostimulation is at best limited to 1 mm.

This interdisciplinary master’s project aims to overcome this limitation and develop a large FOV system with capability to excite individual neurons on an ultra-large FOV. We will do that by using clever combinations of pulse dispersion and multibeam delivery schemes. As part of the project, the student will gain hands-on experience with powerful infrared lasers, optical design, and nonlinear optics. The student will also be trained in the concepts of optogenetic photostimulation and neuronal imaging.

Since the discovery of the 125 GeV Higgs boson at the ATLAS and CMS experiments, a crucial part of the LHC research program has been to investigate the properties of the Higgs boson and establish if they are in agreement with the predictions of the Standard Model (SM). Two key aspects of the SM Higgs mechanism are the tri-linear (𝜆_3) and quartic (𝜆_4) self-coupling constants, which play a crucial role in the electroweak symmetry breaking mechanism and determine the shape of the Higgs field potential. The search for triple Higgs boson production (HHH) provides a unique dependence on 𝜆_4 and a dependence on 𝜆_3, as well as sensitivity to Beyond SM (BSM) physics with extended scalar sectors. The student will contribute to the search of this process in the final state with 4 b-jets and 2 tau-leptons for the first time in ATLAS, focusing on the optimisation of the reconstruction of the Higgs boson’s mass using machine learning, e.g. Symmetry Preserving Attention Networks (SPA-Net), and comparing the results obtained using other reconstruction techniques.

The correct identification of the origin of jets is one of the crucial tasks at LHC experiments in order to complete their ambitious research programs. Recently, the inclusion of advanced deep learning techniques have allowed to improve the jet identification techniques, particularly flavour tagging, to an unprecedented accuracy. However, few attempts have been performed in recent years to identify the charge of the jets. The precise determination of this property is nevertheless pivotal in electroweak and flavour measurements at the high energy frontier and in improving the discovery potential of Beyond Standard Model physics in same-charge quark final states. The successful candidate will develop a new algorithm to accurately measure the charge of the jets with the ATLAS detector. Such an algorithm will be based on the current state-of-the art machine learning techniques, namely graph neural networks and topographs, trained on Monte Carlo simulations. If time allows, the student will also define a strategy to calibrate the expected performance of this new algorithm in simulation versus the LHC data collected by the ATLAS detector during Run-2 and Run-3.

Dark matter remains one of the most compelling and active areas of research in high-energy physics. Numerous astrophysical and cosmological observations, such as the precise measurement of the cosmic microwave background power spectrum, gravitational lensing by galaxy clusters, and galactic rotation curves, provide strong evidence for the existence of a new form of matter that does not interact with light but accounts for approximately 24% of the total energy in the Universe. Despite this indirect evidence, the particle nature of dark matter has yet to be confirmed. Searches for dark matter at the LHC assume it can be produced in proton-proton collisions, offering a unique opportunity to probe its properties. The successful candidate will develop a strategy to search for dark matter in final states featuring same-sign top-quark pairs. This signature is motivated by dark matter models that predict flavour-violating interactions between dark matter and Standard Model particles. The project will focus on implementing the relevant theory models in the ATLAS simulation framework and optimizing the search strategy using machine learning techniques and observables sensitive to the forward-backward asymmetry in same-sign top-quark production. Particular emphasis will be placed on the same-sign dilepton channel and, if time and relevant identification algorithms are available, the single-lepton channel.

Many extensions of the Standard Model (SM) predict events containing multiple leptons. In particular, final states with two leptons with the same charge, or three or more leptons serve as an ideal hunting ground for physics beyond the SM (BSM), as corresponding SM backgrounds are relatively rare at the LHC. While many BSM models have probed over the years, fully exploring the vast possible model space becomes unmanageable. We propose a novel and broad model-independent multilepton search in final states containing two same-charge leptons or three leptons of any flavour (electrons, muons and taus). The student will be involved in applying state-of-the-art unsupervised machine learning techniques that allow us to identify interesting events in the data in a model-agnostic way. The student will use Monte Carlo simulation to optimize this search, estimate backgrounds, and eventually evaluate the expected sensitivity assuming the full Run 3 dataset.

Since the discovery of the Higgs boson in 2012, the ATLAS and CMS experiments have tirelessly searched for hints of additional heavier Higgs bosons. Most of these searches assume that such heavy Higgs bosons couple to fermions in a flavour-conserving way (e.g., H->tt). However, there are extensions of the Standard Model (SM) that allow flavour-violating couplings (e.g., H->tc or tu), which could even be dominant, making the current search strategy ineffective. Recently, the first dedicated ATLAS search for such flavour-violating Higgs boson in the multi-lepton and multi-b-jet final state found an intriguing 2.8 σ excess using the full Run 2 dataset. But why limit the flavour-violating coupling to quarks? A natural extension of this search would involve flavour-violating decays of the heavy Higgs boson to leptons (e.g. H->e𝛕, μ𝛕), allowing for even more leptons in the final states. We propose a search for this novel BSM model. The student will use Monte Carlo simulation to optimize this search, estimate backgrounds, and eventually evaluate the expected sensitivity assuming the full Run 3 dataset.

The Biomimetic Systems for Cell Engineering group focuses on developing advanced tools to create more reliable in vitro cell culture models, particularly 3D tissue barrier models. These models mimic the mechanical properties, multi-compartment structure, and complex 3D geometries of the tissue, which have a crucial role for maintaining tissue homeostasis. Using biocompatible hydrogels and techniques such as high-resolution light-based 3D bioprinting, we can fabricate tissue surrogates that replicate the intricate 3D architecture and microenvironment of native tissues, such as the intestinal epithelium and skin. These models promote tissue formation and barrier functionality by incorporating specific biochemical and biomechanical cues.

Our multidisciplinary expertise has enabled the creation of a gut-on-chip model to study flow dynamics on intestinal epithelial barriers and the development of a vessel-on-chip system to replicate the tumor metastatic environment. Recently, we engineered a full-thickness human skin model comprising dermal and epidermal compartments. By integrating endothelial cells and fibroblasts within the dermis, we promoted intercellular crosstalk, enhancing the formation of an early-stage microvascular network.

We seek a motivated student interested in skin tissue engineering with a background in cell biology, bioengineering, immunology, and/or (bio)chemistry, to bring a step forward our skin models towards full dermal endothelialization. The specific aims of the project will be tailored to the student’s scientific interests and skills. The student joining the lab will be trained in experimental design, data analysis, and oral presentation skills; learning basic cell culture, hydrogels’ fabrication and characterization, 3D bioprinting and imaging techniques, to independently perform and track the experiments.

The goal of this master thesis is to develop nanocoatings to improve the hemocompatibility by mimicking endothelium.
Natural endothelium, the lining of blood vessel is the only surface that can modulate the state of blood, allowing coagulation when needed, restricting it to a region, but preventing it for causing negative event. Unfortunately, there is no blood-contacting medical device today capable of this. The consequences in blood-contacting medical devices, range from clot formation, clogging pumps, risk of thrombosis or haemorrhage and even much more devastating when dealing with pediatric oxygenators. Our goal is to devise a radically new concept to interface blood, where a synthetic or hybrid nanocoating is capable of mimicking the most salient aspects that make natural endothelium unique (see: 10.1002/mabi.202400152). This master thesis aims at contributing towards this goal. Embedded in a highly interdisciplinary team of chemists, physicists, bioengineers and biologists, the candidate will develop a nanoscale coating having the ability: (1) to be stealth to blood, adding a cloak of invisibility and preventing activation of coagulation and inflammation. (2) locally modulate activation, so that you can stop clot formation right before it accumulates. (3) Interactive, by exploiting mechanism to trigger the fibrinolytic system and or turning platelets quiescent.
The specific goals of this master thesis are:
(1) Synthesis of antifouling polymer brushes and evaluation of stealth performance
(2) Functionalization with coagulation inhibitors and study their capability to inhibit coagulation
(3) Introduce a mini-fibrinolytic and NO-release system
(4) Implement experiments to probe your coatings
This thesis entails training in advanced polymer synthesis, characterization of nanoscale coatings (XPS, SPR, AFM) and characterization of blood-material interactions at our labs (SPR, basic hemocompatibility studies) as well as through our collaborators in University Clinic Aachen, Germany, ISGlobal Barcelona and Institute of Macromolecular Chemistry Prague.

The goal of this master thesis is to synthesize a small library of amphiphilic comb polymers, study their self-assembly into biomembranes and exploit their heterogeneity to achieve cell-mimetic functions.
Bottom-up synthetic biology proposes the creation of life-like synthetic cells from the self-assembly of natural and synthetic components and it holds promise as a platform to understand biology and to design new micromaterials for biomedicine and drug delivery. Arguably, the synthetic cell membrane is one of the most important parts as in the membrane all interactions (sensing, deformation, communication, cell division, etc) occurs. It necessary to develop new biomimetic vesicles beyond the state-of-the-art liposomes and polymersomes. Our group recently demonstrated that amphiphilic comb polymers consisting of a hydrophilic backbone and hydrophobic side tail assembled into biomimetic vesicles, termed “Combisomes” with superior stability compared to liposomes but that faithfully recapitulate physical properties and dynamics of cell membranes, in spite of their large molecular weight (Wagner, Adv Science, 2022). They could harbor lipids, transmembrane proteins and fuse with cell membranes. Moreover, we elucidated the mechanism of assembly via a combination of biophysical techniques and molecular dynamics simulations. However, how the molecular structure and topology influences the combisome properties remains unexplored but holds promise for the design of precision vesicles.
The specific goals of this thesis are:
(1) Synthesis of backbone of the comb by copolymerization of of N,N-dimethylaminio acrylamide and a betaine-acrylamide with different proportions and degrees of polymerization
(2) Synthesis of supramolecular comb polymers using the backbone from (1) and different hydrophobic ligands including dialkyl phosphates (C8-16) and dendronized ones.
(3) Modelling of how the randomness in the sequence can be exploited to achieve emergent properties such as fusion with cells, or engulfment.
(3) Self-assembly into vesicles and study their main physical properties (thickness, flexibility, stability, lateral mobility).
This thesis will provide training in advanced controlled radical polymerization, molecular self-assembly, optical, electron and force microscopies and biophysical techniques based on them. It will develop completely new vesicles for synthetic biology and nanomedicine.

Human fertility is quite ineffective, only one third of conceptions lead to a live birth. One third of the embryos never implants and the other third is lost right around implantation, making implantation a bottleneck for human fertility. The Bioengineering in Reproductive Health laboratory is dedicated to understanding the determining factors setting a successful implantation by looking at the metabolism and the forces embryos apply during implantation.
The project aims at understanding the interaction of embryos with their surroundings allowing for invasion and symmetry breaking leading to distinct specialized tissues giving rise to the placenta and the developing organism. The master student will employ methods from molecular biology, embryo culture and microfabrication, they will use advanced imaging techniques and perform quantitative data analysis.
We are looking for a student with a background in Bioengineering, Embryology, Cell Biology, or Biophysics, who is interested in understanding the fundamental process of embryo implantation, metabolism and mechanobiology. The detailed Master’s project is flexible and will be designed together with the successful candidate based on their interests within our research lines. They will acquire basic competences related to the experimental work in a multidisciplinary lab on reproductive health.

Embryonic development requires a thorough regulation of cell proliferation, cell cycle dynamics and cell differentiation. This can be achieved by the spatiotemporal control of the cell cycle length and the mode of stem cell division. In the nervous system, neural stem cells divide symmetrically, generating two identical cells, either stem cells or neurons, or asymmetrically, originating another stem cell and a cell committed to neural differentiation or neuronal precursor. The mechanisms that drive asymmetry during cell division and cell fate induction have been long-standing questions in developmental biology. In recent years, damaged or deleterious cellular components have been described as a source of asymmetry during cell division and an inductor of differentiation. Damaged ubiquitinated proteins targeted for degradation are indeed asymmetrically distributed in mouse dividing neural stem cells. They are segregated to the neuronal precursors to ensure the fitness of their sister stem cells.
Our goal is to explore the role of damaged proteins during zebrafish hindbrain development, as well as the mechanisms implicated. The hindbrain, the most evolutionary conserved part of the brain, harbors different stem cell populations that divide in distinct manners. We will assess the presence or absence of asymmetric segregation of ubiquitinated proteins in said populations, perform functional analyses of the impact of ubiquitinated protein load on their dynamics, as well as transcriptomic experiments to determine what pathways are triggered in these circumstances. Finally, should time allow it, we will explore the impact of other cellular stresses, such as DNA damage, previously linked to cell differentiation in the brain, to hindbrain development.
In all, the candidate will learn high resolution 4D imaging of live embryos, gene expression analysis techniques, like in situ hybridization and RNA-sequencing, and the generation of genetic constructs and zebrafish mutants, using conventional cloning methods and CRISPR-Cas9 technology.

Investigating Epistasis Between Fertility and Disease Using UK Biobank Data
Epistasis, or interactions between genetic variants, plays a vital role in shaping complex traits and diseases. This study aims to explore how genetic interactions influence fertility traits, such as age at first birth, number of children, and reproductive health, and their associations with diseases. Understanding these relationships can illuminate the genetic mechanisms underlying reproductive health and their evolutionary and health-related implications.
The UK Biobank, with its vast dataset of over 500,000 participants, offers an unparalleled resource for such an analysis. Its comprehensive genotype and phenotype data, combined with detailed reproductive and health records, enable the detection of epistatic interactions. Previous studies leveraging this resource have successfully uncovered epistatic interactions in conditions such as Alzheimer’s disease and COVID-19, demonstrating the feasibility and value of this approach.
This project will perform genome-wide epistasis testing using advanced computational tools like BOOST and VariantSpark. By analyzing fertility traits alongside disease phenotypes, the study will identify significant gene-gene interactions and validate these findings through replication in independent cohorts and functional analysis. Statistical rigor will be ensured by controlling for confounders, addressing population stratification, and correcting for multiple testing.
The expected outcomes include the discovery of novel epistatic interactions between fertility and disease-related genes, providing insights into the genetic basis of reproductive traits and their evolutionary trade-offs. These findings have the potential to enhance our understanding of the genetic architecture underlying human fitness and health, contributing to fields such as evolutionary biology and complex disease research.

Cells are constantly challenged by fluctuations in their environment and they must rapidly rewire their internal circuitry, meeting new demands without losing their identity to maximize fitness. Failure to adapt can lead to decreased cellular function, impaired survival, and potentially cell death, ultimately compromising viability.

Our lab seeks to unravel the molecular mechanisms behind these adaptive processes, focusing on signaling pathways and adaptive responses that shape cell fate decisions. Our multidisciplinary approach combines cutting-edge techniques in proteomics, genomics, transcriptomics, and single-cell analyses to decode the language of cellular adaptation.
PhD candidates will have the opportunity to engage in innovative research opportunities:
From discovering novel gene functions essential for stress adaptation through genetic screens (CRISPR-screens in yeast or mammals) to biochemical identification of novel targets controlled by stress-activated protein kinases and define their impact in cell physiology. Together, we aim to define novel mechanisms controlling cellular adaptation. We leverage cutting-edge single-cell RNA sequencing (scRNA-seq), to uncover the heterogeneity in the adaptive response. We then link these molecular profiles to phenotypic profiling to gain and gain insights into the diverse cellular strategies employed of adaptive strategies.

Join our stimulating and collaborative scientific environment, where you will work alongside a multidisciplinary team and engage with international collaborators. By understanding how cells mount adaptive responses, we aim to unlock new insights into health and disease.

The Biomimetic Systems for Cell Engineering Lab focuses on developing advanced in vitro cell culture systems that provide a more complex environment for cells than traditional 2D plastic petri dishes. In recent years, the group has established a research line centered on studying 2D monolayers derived from intestinal organoids. Within this framework, we have successfully optimized 2D cultures, integrated them into 3D scaffolds, and exposed them to gradients mimicking those involved in establishing the crypt-villus axis.
Recently, we set a wound-healing model that incorporates the stromal compartment and we utilized microcontact printing of Wnt proteins to control the size and positioning of intestinal crypts. Additionally, we have extended our research to include Apc knockout (KO) monolayers, enabling us to study primary cancer-derived monolayers in vitro. While numerous studies have explored how epithelial cells migrate from the crypt to the villus using in vivo and in vitromodels, which allow for single-cell resolution, little is known about how this migration occurs in pathological contexts, such as in the Apc KO model.
This project aims to establish a wound-healing model of Apc KO monolayers to investigate intestinal epithelial migration under pathological conditions. Specifically, the project will focus on (i) characterizing Apc KO monolayers and (ii) studying cell migration from both collective and single-cell perspectives.
The student participating in this project will gain hands-on experience in isolating intestinal crypts, culturing organoids, and growing organoid-derived intestinal monolayers. Beyond cell culture, the student will develop expertise in techniques such as immunostaining, RT-qPCR, fluorescence microscopy, and live-cell imaging. Additionally, the student will apply image analysis techniques to quantify and interpret experimental data.

The development of embryo models based on human pluripotent stem cells (hPSCs) is revolutionizing our understanding of early human embryogenesis. Under tailored microenvironmental cues, hPSC colonies exhibit a remarkable capacity for self-assembly, forming cellular systems that replicate key aspects of developmental processes inaccessible for direct observation in vivo. In this Master’s project, the student will contribute to the development of embryoids by integrating human pluripotent stem cells (hPSCs) with biochemical, mechanical, and optogenetic manipulations. These tools will be applied to study fundamental processes in early embryogenesis such as symmetry breaking and axis formation during human gastrulation. The work will involve advanced hPSC technology, optogenetic tools, micropatterning, mechanobiological characterization, and live-cell microscopy.

Physical forces impact biological function. This is particularly relevant in the intestinal epithelium, the fastest self-renewing tissue in the body. Rapid self-renewal is enabled by stem cells that reside at the bottom of highly curved invaginations called crypts. To maintain homeostasis, stem cells constantly divide, giving rise to new cells that proliferate further, differentiate, and migrate. How the distinct functions involved in intestinal self-renewal are coordinated to ensure homeostasis is poorly understood. In this project we will test the hypothesis that the forces experienced by cell nuclei govern cell division, migration and differentiation. We will test this hypothesis using intestinal organoids as model systems. The MSc student will use technologies developed in our group (Perez-González et al, Nature Cell Biology, 2021) to map cellular and nuclear forces with single cell resolution. We will then study the mechanistic relationship between these forces and the cell division rates and migration velocity. We expect that this project will contribute to explain how physical forces govern tissue homeostasis.

Understanding Earth’s biodiversity and responsibly administrating its resources is among the top scientific and social challenges of this century. The Earth BioGenome Project (EBP) aims to sequence, catalog and characterize the genomes of all of Earth’s eukaryotic biodiversity over a period of 10 years (https://www.pnas.org/content/115/17/4325). The outcomes of the EBP will inform a broad range of major issues facing humankind, such as the impact of climate change on biodiversity, the conservation of endangered species and ecosystems, and the preservation and enhancement of ecosystem services. It will contribute to our understanding of biology, ecology and evolution, and will facilitate advances in agriculture, medicine and in the industries based on life: it will, among others, help to discover new medicinal resources for human health, enhance control of pandemics, to identify new genetic variants for improving agriculture, and to discover novel biomaterials and new energy sources, among others.
The value of the genome sequence depends largely on the precise identification of genes. The aim of the research project is to contribute to the development of gene annotation pipelines that produces high quality gene annotations that can be efficiently scaled to more than one million species. Our group has a long-standing interest in gene annotation. Roderic Guigo developed one of the first computational methods to predict genes in genomic sequences, which has been widely used to annotate genomes during the past years. On the other hand, we are part of GENCODE, which aims to produce the reference annotation of the human genome. Within GENCODE we have developed experimental protocols to efficiently produce full-lengh RNA sequences.
Within the framework of this program, there are three possible specific projects
1. Methods for genome annotation based on long read RNAseq (experimental/computational)
2. Methods for selenoprotein prediction and annotation (bioinformatics)
3. Prediction high quality complete annotations (including lncRNAs) using Machine learning (ie. structured decoding from learning embedding) and large language models (strongly computational)

This ERC-funded project aims to develop an RNA-based gene writing technology. RNA will be used. We are combining bioprospecting with generative AI approaches to screen novel writers.

This project will provide a training on
1) Engineering biology. This project lies at the intersection of biological hardware and AI software to design the next generation of genome engineering technologies.
2) Research with tech transfer potencial. We plan to start a liver in vivo gene writing program in one specific medical indication (in collaboration with one of the synbio lab spin offs).

Zinc excess and its consequences on mitochondrial physiology underlies the mechanism of harmful processes that affect human health such as neurodegeneration. This is a multidisciplinary research project that focuses on the study of mitochondria zinc fluxes and their consequences, which are essential to understand and prevent certain deleterious cellular processes that are relevant in the nervous system. The methodology involves cell culture, live cell imaging and detection, confocal microscopy and molecular biology techniques.

We are interested in the functional characterization of novel genetic, molecular and cellular mechanisms underlying the pathogenesis of neurological disorders, with focus on hemiplegic migraine (HM), epileptic encephalopathy and hereditary forms of ataxia. In this sense, we have identified new genetic alterations in the CACNA1A gene (coding for the pore forming alpha 1A subunit of the high-voltage activated CaV2.1 (P/Q) calcium channel) in a clinical background of these neurological disorders. They affect not just the structure and the biophysical features of CaV2.1 channels, but also their modulation by regulatory proteins (G proteins and SNARE proteins of the vesicle docking/fusion machinery). We also study the regulation by glycosilation of the activity and membrane trafficking of CaV2.1 and mechanosensitive Piezo channels, as Phosphomannomutase Deficiency (PMM2-CDG) (the most frequent congenital disorder of N-linked glycosylation (CDG)) includes neurological alterations triggered by mild cranial trauma and shared with patients carrying CACNA1A mutations.
In an international collaboration we are now developing CaV2.1 selective tool molecules capable of reversing the functional consequences of both CACNA1A human mutations linked to HM and channel hypoglycosilation, and exploring their potential to produce a treatment for these neurological pathologies and migraine in general.
For our research we employ techniques of molecular and cellular biology in combination with 3D-structural modelling, electrophysiology and calcium imaging to study ion channels activity in heterologous expression systems and neurons from wild-type and disease model knock-in mice. In vivo analyis is also planned by using C. elegans to evaluate the effect of these CaV2.1 modulators on enhanced neurotransmission due to CACNA1A malfunction.

While the visualization of quantum dynamics has seen significant development and has established itself as an industry, the realm of sonification, the process of translating quantum dynamics into sounds, remains relatively unexplored. This involves the generation of sounds, either digitally (via classical or quantum computer) or analogically (using musical instruments) derived from simulations or laboratory data across diverse quantum systems.

The Master’s project is profoundly interdisciplinary, encompassing: a) the fundamentals of quantum mechanics, with a focus on the theory of individual quantum trajectories, quantum many-body physics, and quantum many-body dynamics; b) diverse approaches to mapping quantum data to sound; c) the utilization of specialized audio programs (such as SuperCollider) to translate data into various sound parameters; and d) foundational knowledge in acoustics, music theory, and data sonification.

The ideal candidate will possess a solid background in quantum physics and computer simulations. A basic understanding of acoustics and music theory is required, coupled with an openness to experimental music research. While experience in audio synthesis, coding (with various audio programming environments), and algorithmic composition is highly advantageous, it is not mandatory.

Project Title:
Kinetic Study of Multivalent Drugs Uptake in Live Cells

Introduction:
Multivalent drugs, designed to engage multiple receptors simultaneously, represent a powerful approach in targeted therapies for complex diseases such as cancer and neurodegenerative disorders. Despite their potential, understanding the kinetics of multivalent drug uptake, cellular endocytosis, and intracellular trafficking in live cells remains limited. Key factors, such as receptor density, drug valency, and cellular dynamics, significantly impact their efficacy. This project aims to study the real-time uptake, endocytosis, and transport of multivalent drugs within cells, providing insights to optimise their design and therapeutic performance.

Objectives:

1. Quantify the kinetics of drug-receptor binding, endocytosis, and cellular uptake.
2. Explore the impact of drug parameters (valency, size, shape) on uptake efficiency and trafficking pathways.
3. Model intracellular trafficking dynamics using computational tools.
4. Correlate uptake kinetics and trafficking behaviour with receptor clustering and downstream biological effects.

Methodology: This project combines experimental imaging and computational modelling. Fluorescently labelled multivalent drugs will be tracked in live cells using advanced microscopy (e.g., confocal and single-particle tracking). Kinetic parameters for binding, endocytosis, and trafficking will be derived from quantitative analyses of imaging data. Computational models employing ordinary differential equations (ODEs) and nonlinear dynamics algorithms will predict intracellular trafficking behaviours and validate experimental findings.

Significance: This project will uncover how multivalent drugs navigate endocytosis and intracellular trafficking pathways, advancing their therapeutic potential. The findings will contribute to developing precision-targeted therapies for diseases like Alzheimer’s, immunological disorders, and cancer.

About the Group:
The Molecular Bionics Group is highly interdisciplinary, merging expertise in physics, chemistry, biology, mathematics, and data science to study biological systems and develop bioengineered therapies. We seek life scientists eager to train in data science and non-linear dynamics or physical scientists willing to train in cell biology, endocytosis, and advanced microscopy.

The methionine cycle is a fundamental cellular pathway responsible for metabolizing and regenerating methionine. Disruptions in the proper flow of metabolites through this cycle are characteristic of certain inborn metabolic disorders, which manifest in severe neurological and muscular dysfunctions in children. Interestingly, the shared metabolic disruptions in four of these inherited disorders offer an opportunity for a unified therapeutic strategy.

This project aims to computationally and experimentally validate a novel therapeutic proposal targeting these disorders. The student will first refine and expand existing mathematical models of the methionine cycle, integrating them with experimental data. Next, these enhanced models will be used to simulate disease-specific scenarios for these four distinct inherited metabolic disorders. The final stage will involve leveraging the models to experimentally evaluate potential therapeutic interventions aimed at restoring methionine cycle balance.

The outcomes of this project are expected to evaluate the therapeutic potential of the unified approach for these disorders. Additionally, the models developed could hold significant clinical value, supporting personalized medicine strategies tailored to individual patient profiles.

The project will be jointly supervised by Dr. Rosa Martinez-Corral (CRG, Barcelona Collaboratorium) and Dr. Sergi Aranda (CRG). The student will gain comprehensive training in computational and experimental approaches, with specific objectives to:

Expand knowledge in computational biology and systems modelling.
Develop technical skills in mathematical modelling, data analysis, and experimental techniques.
Foster intellectual growth in addressing complex biological questions through creative, interdisciplinary methods.
The trainee will actively participate in weekly lab meetings, and seminar series at the Genome Biology Program at CRG and at the Collaboratorium, ensuring an engaging and collaborative learning environment.

Research project summary: The tumour suppressor gene p53 is mutated in half of the human cancers, and there is still extensive morbidity and mortality associated with cancers bearing p53 mutations. Given the difficulties in developing strategies for targeting wild-type or mutant p53, further understanding of its basic biology is required for successful clinical translation. Recent studies, including ours, have challenged the previously understood model of how the p53 gene is involved in tumour suppression. We found that several p53 activated target genes implicated in DNA repair have critical functions in suppressing lymphoma/leukaemia development. Based on this observation, we hypothesise that coordination of DNA damage repair is the most critical mechanism by which p53 suppresses tumour development. The present PhD project focuses on understanding the complexity of the p53 network in tumour suppression in different contexts, in order to determine which p53 downstream function should be targeted for treatment of different tumour types, without targeting p53 itself.
Training objectives: The role will involve the use of a wide variety of experimental techniques, including tissue/tumour pathology, CRISPR-Cas9 gene-editing technology, molecular biology, cell culture and flow cytometry. In addition, successful candidate will have access to a wide range of academic activities; UPF and Barcelona Biomedical Research Park seminars, conferences and symposia.

Environmental physical and chemical cues control essential cell processes like
differentiation, cycle progression, migration, and death. Accordingly, cell responses to
these signals are at the core of both physiological (wound repair, muscle contraction)
and pathological conditions (metastatic cancer invasion, fibrosis). During tissue
invasion, cells must simultaneously process biochemical signals and adapt to physical
constraints by modifying their shape and migration strategies. Our work has revealed
that Piezo1 mechanosensitive ion channels orchestrate this complex response by
balancing different types of cell-matrix adhesions – focal adhesions required for
migration and reticular adhesions necessary for division. Crucially, reticular adhesions
also serve as hubs for receptor endocytosis, positioning Piezo1 as a master regulator
that integrates mechanical and chemical signals. Using CRISPR-edited cells,
microfabricated environments, and advanced imaging, we will investigate how Piezo1
controls the mechanical balance between adhesion types and how this balance directs
cell migration during chemotaxis, a key feature of metastatic invasion. This research will
reveal fundamental mechanisms controlling cell behavior during cancer progression and
could identify new therapeutic strategies targeting the mechanical aspects of
metastasis, addressing a major challenge in cancer treatment.

The brain microenvironment is tightly regulated to allow proper neuronal activity. To achieve this, the brain vasculature carefully controls what is transported from the blood into the brain and to what extent. While we have a clear understanding of the vascular mechanisms which transport the required components to support neuronal activity, there is a lot still to learn about how neuronal activity itself affects the selectivity and magnitude of transport across the brain vasculature. Such knowledge will allow us to better understand how the brain meets energy requirements, how diseases such as Alzheimer’s disease or epilepsy affect vascular transport, and how we may engineer nanoparticle-based strategies for enhanced therapeutic delivery.
This project will therefore examine how neuronal activation affects the endocytic rate of membrane proteins in brain endothelial cells, and how this impacts nanoparticle entry into the brain.
To achieve these goals, this project will develop a 3D-invitro model of the brain vasculature incorporating optogenetically-modified neurons to control neuronal activity through laser excitation. This system will be employed to assess the effect of neuronal activity on the endocytic rate of cell-membrane proteins through high-throughput quantitative proteomics, and how this impacts the internalization and transport of brain-targeted polymeric nanoparticles across brain endothelial cells.
The knowledge acquired during this project will form the basis of future projects translating the techniques to in vivo models, thereby providing a deeper understanding of how neuronal activity affects endothelial membrane dynamics, and how to exploit these to engineer nanoparticle-based therapy-delivery systems with higher targeting precision and better efficiency.

Haematopoietic Stem Cells (HSCs) predominantly remain in a quiescent state, dividing occasionally to self-renew and maintain the stem cell reservoir. This balance is essential for the continuous replenishment of mature blood cells. Their finely tuned metabolism dynamically shifts between glycolysis and oxidative phosphorylation, adapting to the conditions of their microenvironment. Disruptions in the mechanisms that regulate mitochondrial genome stability and function can destabilise the equilibrium between self-renewal and differentiation. Mutations in mitochondrial DNA (mtDNA) may impair organelle quality control, leading to challenges in HSC maintenance and differentiation, particularly in individuals with mitochondrial diseases.

In this study we will investigate the effects of mtDNA instability on HSC function through various models including preclinical models lacking mtDNA proofreading capacity, and blood samples from patients with mitochondrial diseases. We will employ methods such as mtDNA mutational load analysis, ex vivo CRISPR-Cas9 editing in haematopoietic stem and progenitor cells, and pharmacological or genetic modulation of stem cell fate in both mouse and human samples. Specialised methods in mitochondrial biology will be employed to investigate the structure, function, and regulation of mitochondria and their roles in key cellular processes such as metabolism and cell signalling. The student will take part in various training courses designed to provide a comprehensive understanding of the advanced research techniques available at the IRB Barcelona.

By examining the relationship between mtDNA dynamics, haematopoiesis, and immune homeostasis, this research aims to elucidate the underlying mechanisms of mitochondrial diseases and their impact on stem cell biology.

Protecting hematopoietic stem cells from inflammatory stress

Alterations in immune functions not only impair our organism defenses to pathogens but also underlie diseases such as cancer, cardiovascular, metabolic, and neurodegenerative disorders. We focus our work on NFAT5, a transcription factor that regulates innate and adaptive immunity in different scenarios, such as inflammation, graft rejection, tumor progression and viral infection.

Our recent work shows that NFAT5 controls the expression of type I interferon (IFN-I) in mature immune cells in response to infection, and attenuates the sensitivity of hematopoietic stem cells (HSC) to this cytokine under hematopoietic stress (Huerga Encabo et al. 2020 J Exp Med; Traveset et al., 2024, Blood Advances). These functions converge in helping HSC to maintain long-term stemness. A correct functioning of hematopoiesis is fundamental to maintain a balanced and well-tuned immune system, and to ensure its continued renewal. In this MSc project we will study immunological and hematopoietic mechanisms that protect HSC from inflammatory signals that promote cellular aging.

Recent key publications: Traveset et al 2024 Blood Advances; Lunazzi et al 2021 Journal of Immunology; Huerga Encabo et al 2020 Journal of Experimental Medicine; Aramburu and Lopez-Rodriguez 2019 Frontiers in Immunology; Buxadé et al 2018 Journal of Experimental Medicine; Tellechea et al 2018 Journal of Immunology.

The human microbiome is a series of distinct communities of bacteria, fungi, viruses, archaea, protists, and other microorganisms, whose compositions vary depending on environmental conditions. Different sites of the human body can be seen as unique biomes, with drastically different environments and nutrient availabilities, which in turn promote different communities. Yet even within a particular body site, the microbiome composition can be highly variable between individuals in different states of health, with distinct lifestyles, or due to a number of other factors. In this project, the student will get exposed to varios projects related with the human oral and gut microbiomes in relation to several diseases and conditions, including cystic fibrosis, colon cancer, or Alzheimer disease. The student will learn basic techniques related to DNA extraction, amplification and sequencing, as well as culture and identification of different micro-organisms. He/She will also get involved in the analysis and interpretation of sequencing data. The balance between experimental or computational work during the stage will depend on the background and interest of the student.

Ultrasound (US) imaging is a key technology in medical practice that has undergone outstanding improvements in spatial and temporal resolution over the last 20 years. Commercial ultrasound transducers allow non-invasive, real-time 3D imaging of deep tissues enabling diagnostic and therapeutic applications in areas such as cardiovascular disease. However, current ultrasonic transducers are bulky and expensive, which limits its applicability and accessibility. The development of cheap and wearable US transducers could hence allow continuous monitoring of critical medical parameters that are currently inaccessible in a continuous manner. To this end, we will explore microfabrication of ultrasonic transducers in thin, flexible substrates to overcome state-of-the-art limitations in sensitivity and contrast. The execution of this Project will involve some of the following activities: ultrasonic device simulation and design, clean-room microfabrication (e-beam evaporation, UV-photolitography, wet etching and reactive ion etching), and ultrasonic transducer electrical characterization.

Our lab studies the interplay between genetic mutations and pro-inflammatory insults that promote cancer development and metastatic progression, with a focus on pancreatic and liver cancers, two clinical challenges in need of more effective early detection and treatment strategies. As genetic and environmental drivers of cancer act by co-opting physiological immune responses that normally safeguard normal tissue homeostasis (eg wound healing/regeneration, anti-tumor immunity), we combine bulk/single-cell epigenomic profiling and flexible disease models to expose molecular and cellular traits that are unique to tissues undergoing malignant growth, and apply functional genomics tools (RNAi/CRISPR) to pinpoint the key mechanisms responsible for fueling tumor evolution. The available Master projects aim to characterize and perturb cellular states and cell-cell crosstalk networks that are selectively induced during tumor development and metastasis (eg: Alonso-Curbelo et al. Nature 2021; Burdziak*, Alonso-Curbelo* et al. Science 2023), with a focus on how aging alters immune responses and tumor-host crosstalk to promote cancer evolution:
1. Computational mining of aging-associated immune programs (pancreas, metastatic niches) in bulk and single-cell sequencing datasets.
2. Genetic tagging of cellular states distinguishing pro-tumor vs physiological ecosystems.
3. Functional dissection of their defining molecular programs.

Through this opportunity, the student will receive training in general cancer biology, molecular cloning, functional validation approaches (RNAi/CRISPR-mediated genetic perturbations), histology (immunofluorescence/immunohistochemistry), flow cytometry, organoid culture, cell lines and primary immune cells; as well as on experimental design, data analysis and reporting. The student will also work with our team to set up innovative experimental pipelines and will contribute to a constructive and stimulating working environment.

The optoelectronic properties of 2D materials are at the forefront of condensed matter research, bridging fundamental physics with innovative device applications for future telecommunication technologies. Understanding how light interacts with these materials is key to unlocking their potential. The ability of light to generate currents (photocurrent) or modify conductivity (photoconductivity) offers a direct window into the electronic structure, providing additional information and enhanced sensitivity compared to traditional optical (scattering) methods.
A variety of mechanisms governs photo-transport in 2D materials. In metallic states, light absorption can raise the electron temperature altering the conductivity (bolometric effect), while localized illumination can create temperature hotspots that drive photocurrents via the photothermoelectric effect. In insulating states, light with energy above the bandgap generates electron-hole pairs, which can be separated by in-plane electric fields to produce currents (photovoltaic effect). Recently, new photocurrent mechanisms driven by intrinsic symmetry breaking in the crystal (photogalvanic effects) have also started to attract attention, adding further complexity and richness to the field.
Exploring and controlling these optoelectronic responses requires various experimental techniques—such as photocurrent, photoconductivity, and double-modulation methods. However, choosing the right method and the right parameter space for the measurement can be challenging, due to the lack of comprehensive guidelines for addressing artefacts, material properties, device configuration.
In this 9-month project, the student will first fabricate high-quality devices and then systematically compare different photo-transport measurement schemes using bilayer graphene as a test platform. With its well-characterized properties and tunable band structure, bilayer graphene offers an ideal model for studying mid-infrared photoresponses in both metallic and insulating phases. Through this work, the student will not only master advanced optoelectronic characterization techniques but also create a practical guide to help researchers choose the most effective methods for their experiments—providing valuable insights that will have a broad impact on the field.

To study the interactions between polaritonic resonances in two-dimensional materials and the vibrational mode of gases, it is necessary to build a compact and broadband setup. This project would consist of aligning a broadband source and interferometer whose operation ranges between the near-infrared and far-infrared range and owing to the broadband absorption spectrum of graphene, this would lead to high broadband detection of gas fingerprints, which is currently missing in commercially available devices. We will automatize the injection of the evaluated gases into the mixture. We will perform gas detection measurements and use a machine learning algorithm to identify the detected gases and determine their concentrations and percentages in the mixture.

In condensed matter physics, vacuum field fluctuations usually have negligible effects. In systems where collective excitations dominate, this is no longer true, and enhanced vacuum fields can significantly amplify electron-photon interactions (1). In that realm, strong light-matter coupling between mesoscopic systems and cavities have garnered significant interest, for theoretical prediction of cavity-enhanced exciton transport, polaritonic-enabled electron-phonon coupling, enhancement of superconductivity, topological properties or control of local interactions in strongly correlated systems. Recent experiments have used cavities for strong light-matter interactions in the integer (2) and fractional quantum hall effect regime (3). In the strong coupling regime, 2D materials emerged as a material of choice for their tuneable phase diagram and possibilities to incorporate sub-wavelength cavities directly within a heterostructure (4, 5). The project aims to enhance the effective interaction of 2D materials with THz and mid-IR radiation, exploring the coupling of magnetoplasmons with cavities under quantizing magnetic fields.

The electromagnetic field vacuum fluctuations are one of the key features of quantum field theory and have significant implications for our understanding of nature at all levels: from the atomic (Lamb shift in hydrogen atom) to the fundamental structure of the universe (dark energy is hypothetically related to the vacuum field fluctuations). The proposed project is aimed at harnessing the virtual vacuum field photons via their confinement in split-ring resonators [1]. This involves finite-element simulations of split-ring resonators of a specific geometry, their fabrication by means of optical and electron beam lithography and further testing with the available spectroscopy techniques. Further these confined virtual photons may be used to tackle new ground states in the quantum paraelectric SrTiO3 [2, 3].
[1] Appugliese et al., Science, 2022, Vol 375, Issue 6584, pp. 1030-1034
[2] Ashida et al., Physical Review X, 2020, Vol 10, Issue 4, pp. 041027
[3] Curtis et al., Phys. Rev. Research, 2023, Vol 5, Issue 4, pp. 043118

Can we ‘see’ an individual molecule emitting a single photon and tell what colour it is?

The Atomic Manipulation and Spectroscopy group (ICN2) is currently setting up a new photon – scanning probe microscope laboratory owing the unprecedented capability to characterize light-matter interactions with atom-scale spatial precision, and simultaneous picosecond temporal and spectral resolution (1). Within this context, the project proposes a dual scientific and technologic objective: scientifically, it aims to detect single-photon emission from individual molecular quantum dots (2), for the first time combining both temporal and energetic resolution. Technologically, the student will participate in the challenging setting up and commissioning of the state-of-the-art instrumentation in the new lab, including femtosecond-pulsed and narrow bandwidth lasers, an ultra-high vacuum scanning tunnelling microscope operating at 5K and a spectrometer equipped with slow (CCD) and ultra-fast (streak) cameras.

Fundamental understanding of ultra-fast physical mechanisms underlying excitonic light emission from semiconducting nanomaterials (3), as sought in the present, is essential for developing optoelectronic devices for next-generation quantum technologies.

(1) https://ams.icn2.cat/research/photon-nanoscopies/
(2) L. Zhang et al., Nat. Commun. 8, 580 (2017).
(3) R. Gutzler et al., Nat. Rev. Phys. 3, 441-453 (2021).

The student will work with nanostructures based on 2D nanomaterials for Energy and Environmental applications. The student will use the advanced tools offered at the Joint Electron Microscopt Center at ALBA Synchrotron (JEMCA) to analyze at an atomic scale these materials with electrocatalytic properties. Once this challenge is met, it will create atomic models of the structures that will allow us to understand the catalytic properties of these materials. The student will participate in an interdisciplinary project with a coordinated network for the development of new materials for new energy sources and their storage. The work will include the development of 3D atomic models and their simulation to extract the properties of materials. In-situ experiments will be prepared in the working conditions during which it is intended to see the reactions on a sub-nanometer scale. Duties: 1) Participate in an interdisciplinary project with state-of-the-art nanomaterials for future applications in energy and the environment (creation of hydrogen from H2O and fuels from CO2). 2) Acquire knowledge in transmission electron microscopy at the atomic scale. 3) Create atomic models of structures and obtain their simulations of their properties. 4) Develop in-situ experiments under working conditions.The student will work with nanostructures based on 2D nanomaterials for Energy and Environmental applications.

Nanotechnology has had a profound impact on various fields, including materials science, electronics, medicine, and energy production. To gain a comprehensive understanding of nanomaterials and optimize their properties, it is essential to characterize their structure and composition at the atomic scale. Transmission Electron Microscopy (TEM) has emerged as a technique that allows for atomic scale imaging, coupled with spectroscopic methods such as energy dispersive X-ray spectroscopy (EDX) and electron energy loss spectroscopy (EELS), providing spatially resolved information about composition, valence state, and plasmonics and phononics. These techniques permit the correlation of physicochemical properties with atomic structure and composition, leading to a full understanding of nanoscale systems. In this context, the student will focus on the atomic scale characterization of 1D semiconductor materials (nanowires), aiming to unravel the role of atomic arrangement in their properties, such as defect formation and elemental segregation. The project will be in collaboration with research groups from the École Polytechnique Fédérale de Lausanne or the Niels Bohr Institute of the University of Copenhagen, and experimental measurements will be conducted at the Joint Electron Microscopy Center at ALBA Synchrotron (JEMCA) using brand new TEM facilities to analyze materials at sub-nanometer scales. The student will also create 3D atomic models to simulate and interpret the acquired data. As a summary, the student will: Participate as an active member of the Group of Advanced Electron Nanoscopy of ICN2 attending to group meetings and interacting with the rest of the team Adquire knowledge in aberration-corrected TEM and its associated spectroscopies Adquire knowledge in data interpretation and analysis combined with the creation of 3D atomic models and simulations Correlate the experimentally obtained atomic arrangement with the growth mechanisms and physicochemical properties of the nanostructures

Most of the living organisms in our planet are ectotherms, organisms that cannot control their “body” temperature. Yet ectotherms are vulnerable to fluctuations in the ambient temperature. Eukaryotic microorganisms are especially susceptible because their survival relies on more sophisticated membrane dynamics than prokaryotes. Thus, global warming is increasingly challenging the biodiversity of eukaryotic microorganisms and the ecological functions associated to these species. Unfortunately, the lack of knowledge about how species adapt their essential cellular processes to life-threating temperatures, hinders accurate predictions on the climate change impact and frustrates the efforts to develop remedies.

We offer a position for a master student to integrate advanced light and electron microscopy to investigate in situ the biophysical constraints that regulate the viability of cellular processes in front of temperature fluctuations. For this purpose, we will use various species of eukaryotic microorganisms, some of which will be isolated from alpine niches in the Pyrenees. We will exploit the diversity of organisms and quantitative live-cell imaging to deliver mechanistic knowledge.

Understanding the biophysical principles, and the molecular basis associated to them, that constrain eukaryotic microorganisms adaptation to specific thermal niches will allow us to narrow the gap towards understanding the principles that rule the origin and evolution of eukaryotes. The project involves the establishment of new model organisms in the laboratory as well as gene editing techniques. The student will learn super resolution microscopy, particle tracking and image analysis. We will also implement correlative cryo-light cryo-electron tomography methods to measure biophysical constraints in situ.

During the progression of the project the student will acquire a strong expertise in quantitative light microscopy and image analysis. Depending on the student’s skills and interest, the project could also involve modelling of 3D structures or machine learning for image analysis. The lab might provide economical support.

Chromatin missregulation is in the basis of the development of many pathologies, such as cancer, immune or degenerative diseases. Understanding how chromatin profiles change along disease initiation and progression is, thus, essential to diagnose, prognose and design personalized therapies to treat them. In the lab, we have implemented the FLEA-ChIP, a technology specifically developed to identify epigenetic profiles from scarce or limiting samples at high-resolution and sensitivity. In collaboration with the pharma company Oryzon Genomics, we are currently using the FLEA-ChIP technology to profile the epigenetic status of chromatinopathy patients, a set of rare diseases with epigenetic origin. The goal of the current proposal is to identify differences at the chromatin level between healthy and disease donors, as well as to contribute to the evaluation of the FLEA-ChIP technology for the identification of potential specific biomarkers for the different pathologies studied. With this overall goal, the student will use publicly available pipelines and will work in the development of novel computational tools to identify the differences between conditions. With the help of machine learning methods, the student will also work to uncover the best strategy to identify disease-specific epigenetic biomarkers. A part from the tasks directly related to the project, the student will regularly participate in the meetings and conferences held at the CRG. With the goal of developing their interdisciplinary skills, the student will also have access to general training on scientific writing and presentations and time-management courses, among others.

We are seeking a master’s student to join our project on exploring microorganisms of high mountain lakes in the Pyrenees using long-read sequencing (pyrisentinel.eu). This region, with a warming rate higher than the global average, is a key observatory for the impacts of global change. Approximately 300 Pyrenean lakes have been sampled during summer 2024, which due to their geographical isolation, extreme conditions, and climatic variations, harbor a significant diversity of microorganisms. We aim to provide a detailed insight into the genetic diversity of aquatic microorganisms in the Pyrenees, establishing a benchmark in genomics-based biomonitoring and contributing to the international effort to characterize the global microbiome. Our research seeks to (1) reveal the genetic diversity of aquatic microorganisms in these lakes, (2) identify the drivers of microbial diversity, distribution, and function, and (3) assess the potential of these ecosystems for freshwater bioprospecting.
The student will primarily participate on the analysis of long-read metagenomic data, focusing on microbial diversity profiling, ecosystem comparisons, and gene discovery for biotechnological applications. However, it could also include opportunities for training either in experimental work or deep learning approaches, depending on the student’s interests and initiative. Additionally, there may be opportunities to engage with natural park managers, providing a perspective on the practical applications of the research in biodiversity conservation.

This project aims to elucidate the microtubule network in induced pluripotent stem cells (iPSCs), and how it is remodeled during differentiation of iPSCs into neuroepithelium-like neural rosettes.

The microtubule cytoskeleton provides cells with mechanical support, mediates intracellular transport, positions organelles, and segregates the chromosomes during cell division. These functions are crucial for the formation and maintenance of different types of tissues including the neuroepithelium. Indeed, malfunctioning of the microtubule cytoskeleton has been linked to both impaired neurodevelopment and neurodegeneration. However, how cell type-specific microtubule arrays are organized to carry out different functions is still poorly understood.

The project aims to reveal the overall microtubule network configurations, identify microtubule organizing centers (MTOCs), and describe changes that occur during neural differentiation.

The student will learn the culture and neural differentiation of iPSCs, advanced microscopic imaging techniques, and a range of assays to determine microtubule nucleation, growth and polarity, and composition and function of microtubule organizing centers (MTOCs) such as the centrosome. This will uncover fundamental principles of microtubule network organization in stem cells and derived neural rosettes that are highly relevant for development and disease.

Project 1: Innovative antiviral compounds targeting the main protease of SARS-COV-2. We developed an innovative series of PROTACs, able to recognize and attach to the virus Main Protease (Mpro), a protein without which the virus cannot replicate and infect. Once bound to Mpro, the PROTACs help our own cells to find the intruder viral protein Mpro and destroy it. Hence, at the end, the viral protein is not present in our system anymore and the infection cannot progress. Indeed, we recently obtained proof-of-concept of efficacy of our PROTACs against CoV containing the wild-type Mpro. Then, our antiviral PROTACs should be effective not only against the wild-type Mpro from SARS-CoV-2, but also against all the current and future CoV, including drug-resistant mutants. The goal of this project is to test our PROTACs against the wild type and mutant strains (drug resistant strains) of the main protease of the SARS-CoV-2. In this project we would work in close collaboration with groups at the University of Barcelona and the Rega Institute at KU Leuven.

Project 2: The serine subclass of intramembrane proteases are termed Rhomboid proteases and are found across all kingdoms of life. Among these RHBDL2 and RHBDL4 have been linked to proliferative malignancies such as breast cancer. However, their potential as therapeutic targets remain unexplored to date. Regarding the remaining RHBDLs, 1 and 3, their biological functions and the potential link to disease states are yet to be discovered. This gap of knowledge responds to the lack of substrates and inhibitors to study the RHBDLs. The goal of this project is to develop new fluorogenic substrates for RHBDL4 and 3, which could aid the validation of RHBDL4 as a therapeutic target and the discovery of RHBDL3 biological functions.

The research project focus on developing high performance field effect transistor (FETs) based on graphene nanoribbons (GNRs) grown by on surface synthesis technique. The reduced dimensionality, the atomically-precise edge terminations and morphology of as-synthesized GNRs endow them with tuneable electro-optical properties and unprecedented quality to build FETs. Indeed, theoretical predictions indicate high Ion/Ioff ratio, steep subthreshold swing, low OFF current, high mobility, and fast operation frequency. However, experimental devices suffer of short channel effects (SCE, GNRs length < 50 nm), leading to poor performance. Moreover, current wet-transfer methods lead to non-uniform GNRs distribution, lowering the device yield, and thus limiting their reliability and scalability. In this regard, the group has already optimized not only the growth of a robust two-dimensional (2D) covalent network of long GNRs (> 100 nm) but also a novel dry-transfer method that preserve the GNRs pristine properties via the intercalation of a self-assembled monolayers. Therefore, the project will tackle several key parameters of the device fabrication process such as the carrier injection and transport via device geometry and contact engineering. First, we will vertically stack 2D heterostructures compromising graphene and hBN to enable edge contact for low contact resistance, residues-free for exquisite gating control, and fully passivated devices to avoid degradation. Second, distinct channel lengths will be studied, as the channel length should be at least one third of the gate dielectric to minimize SCEs. Third, low, medium and high work function metals, as well as 2D metals, will be assessed to understand whether or not the Fermi level pinning is governing the carrier injection. Low temperature measurements will be also used to elucidate whether the main transport mechanism is dominated by Schottky barriers or tunnelling, and hence surpass the thermionic limit for its implications on the next generation of FETs.