Biological data is accumulating at an unprecedented rate, escalating the role of data-driven methods in computational drug discovery. The urge to couple biological data to cutting-edge machine learning has spurred developments in data integration and knowledge representation, especially in the form of heterogeneous, multiplex and semantically-rich biological networks. Today, thanks to the propitious rise in knowledge embedding techniques, these large and complex biological networks can be converted to a vector format that suits the majority of machine learning implementations. Indeed, we have generated biological embeddings (i.e. bioactivity signatures) that capture complex relationships between small molecules and other biological entities such as targets or diseases (Duran-Frigola et al. 2020 Nat Biotechnol; Bertoni et al. 2021 Nat Commun). However, only a tiny fraction of the possible chemical space has been so far explored, meaning that most compounds able to modulate biological activities (i.e. drugs) are yet to be discovered. Accordingly, the main objective of this project is to couple our bioactivity signatures to inverse design algorithms to generate new chemical entities with a desired functionality. In particular, we aim at generating new chemical entities (NCEs) to modulate the activity of a specific set of targets, selected from a combination of perturbagen profiles, to revert the pathological state induced by Alzheimer´s disease (AD) and other complex disorders (Pauls et al. 2021 Genome Med. All in all, the incorporation of machine learning methods to the drug discovery process will trigger the development of thousands of novel compounds, finally enabling precision medicine.

The inner ear is one of the most sophisticated sensory organs of the peripheral nervous system and is responsible for the senses of audition and balance. Sensory information is captured by the Hair Cells (HC) that transmit the information to the sensory neurons of the statoacoustic ganglion. Then, the afferent neurons connect to the brain. Mutations in genes responsible for hair cell and neuronal function cause hearing loss or vertigo. Hearing loss is the most prevalent sensory deficit in the world and approximately affects 466 million people, being 34 million children. Around 122 human genes causing non-syndromic hereditary hearing loss when mutated have been identified to date. However, the exact function of many of these genes has not been assessed carefully due to the difficulty of generating mutant animals at large scale. The CRISPR/Cas9 editing system has revolutionized the genetics field by the ability to efficiently mutate or modify any desired gene. Our laboratory is interested in studying inner ear development, gene regulation and hearing loss using the zebrafish and organoids as models systems (see lab publications: https://www.upf.edu/web/alsina_lab/publications) and have set up many techniques for analysing gene function. We have identified a number of regulatory elements involved in gene regulation during otic neurogenesis.
The aim of this proposal is to use the CRISPR/Cas9 methodology to manipulate/delete the regulatory elements and assess their function during inner ear development. We will study neuronal differentiation markers, cell proliferation and cell death in the mutants and perform in vivo imaging of the inner ear in the genomic mutants.
The student will learn techniques of zebrafish manipulation, mRNA injection, gene editing and life imaging.

Alterations in immune functions not only impair our organism defenses to pathogens but also underlie diseases such as cancer or neurodegenerative, cardiovascular and metabolic 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. By uncovering circuits by which immune cells tune their function in diverse scenarios, our work can guide innovative approaches that improve antitumor immunotherapy and anti-pathogen defense.

The proposed MSc research lines connect with our recent finding of a unique transcription mechanism that restrains type I interferon (IFN-I) expression to control antiviral responses while preserving hematopoietic stem cell (HSC) function (Huerga Encabo et al. 2020 J Exp Med). Recent works have established that genomic instability in tumor cells releases DNA to the cytosol, triggering IFN-I induction. This response is dually beneficial to control tumor progression as it promotes tumor cell senescence and alerts specific antitumor immunity. We will apply our experience with tumor models, lineage-specific deficient mice, and cutting edge cell and molecular biology approaches to identify new mechanisms that boost antitumor responses by enhancing IFN-I function at two levels i) improving tumor antigen presentation by dendritic cells to cytotoxic T lymphocytes and ii) promoting tumor cell senescence.

Leading recent publications:

Lunazzi et al., 2021 J Immunol
Huerga Encabo et al., 2020 J Exp Med
Aramburu and López-Rodríguez, 2019 Frontiers Immunol
Buxadé et al., 2018 J Exp Med
Tellechea et al., 2018 J Immunol A
ramburu et al., 2014 Science Signaling
Berga-Bolaños et al., 2013 Proc Natl Acad Sci USA
Buxadé et al., 2012 J Exp Med
Ortells et al., 2012 Nucleic Acids Res.

The student will work with nanostructures based on 2D nanomaterials for applications in Energy and the Environment. The student will use the advanced tools offered by the new ICN2-ALBA synchrotron electron microscopy platform 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.

Quantum technology is supposed to be the biggest revolution that has to happen on the next few years, implying a wide range of fields such as computational and health sciences, energy applications and even the generation of extra-secure communications and encrypting. It will come to stay and deeply change everyone’s life. This project aims to focus on the materials science that is behind quantum computation. However, multiple approaches that compete with each other, (as are carried and sponsored by the main computation companies, i.e. Microsoft, Google, IBM, Intel) are being pursued in order to reach the final common goal of the process, which is the fabrication of a fully functional and commercial quantum computer.
Our research group is closely collaborating with Microsoft on its particular approach to achieve this enormously ambitious goal, which is taking advantage of Majorana pairs as the building blocks for the generation of qubits, which are the fundamental units of information in quantum computation.
According to theory, the configuration that would suit this application the most is the interface between a semiconductor and a superconductor, and an appropriate way to build them is to arrange them in a nanowire, which creates the so-called concept of proximitized nanowires. More concretely, the semiconductor thought to present the best properties would be InSb (although different approaches are being done with InAs, too), and Al or NbTiN are usually used as the superconductor, due to their theoretical transition to topological phase under certain chemical potential and external applied magnetic field conditions. In fact, reaching the material’s topological phase is a fundamental requirement to achieve the Majorana Zero Modes (MZMs), and for them to materialize it is mandatory to create thoroughly ordered and epitaxial heterojunctions, as well as perfectly grown materials (as well as specific requirements for each of the materials implied), that avoid the disorder-based scattering that can prevent the transition or even the failure of the topological regime. As mentioned before, the major project would be devoted to the atomic resolution (S)TEM characterization and further structural and elemental analysis of these devices, as a fundamental part of the global process of optimization of the system for the best achievement of the conditions stated previously.
Incredible efforts are being made to avoid the so unwanted decoherence of the electrons and to directly apply the signatures of MZMs (basically conductance peaks) into real devices for quantum computing, as up to date, the total number and stability of the created qubits is not enough for a functional quantum processor. By the way, these qubits are based on binary gates that control the interaction between the Majorana pairs, and it is actually this interaction what can produce the quantum phenomenon based on the superposition of states. Indeed, direct observation of the theoretical properties of the MZMs is still lacking, which is really challenging but encouraging too, to be able to help to achieve this as soon as possible.
The general goal of the project would be the structural and compositional atomic scale analysis, mainly via STEM and related electron spectroscopy techniques of the primordial materials involved in the creation of the Majorana-based qubits. In this way, the initial data obtain will help to perform a structural and atomistic modelling of these nanostructures, in order to achieve a higher understanding of their nature and how the nanofabrication processes affect their integrity, obtaining a deep knowledge on their growth mechanisms and further physical properties. All the knowledge obtained will eventually give useful feedback to the device’s manufacturers that will help to create higher quality devices and more stable quantum states.

We are ultimately interested in deciphering the mechanisms that control cell cycle progression. Inactivation of the Retinoblastoma protein (RB) leads to unregulated cell cycle progression promoting cell growth, genomic instability and aneuploidy, hallmarks of tumor progression. RB activity is achieved through binding the E2F family of transcription factors. It is well known that a tumor process is very complex, accumulating secondary mutations that eliminate the brakes to the cell cycle. Even though many regulators of the RB-E2F 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.
The candidate will characterize the regulation of the yeast MBF complex (functional homolog of human RB-E2F). The regulated activity of this complex is also essential for the G1/S transition since cells with hyperactive MBF have genomic instability. The candidate will perform 2 whole-genomic screens searching for global regulators of MBF. We have developed a series of reporter strains in the laboratory that are capable of measuring MBF activity in vivo as an YFP/RFP output, either on FACS or on an automated fluorescence microscope platform. The different reporters have different sensitivity to changes in the activity or a different threshold of activity. These reporter strains will be introduced in a yeast KO deletion library, either as individual colonies or as a pool with all the knock outs (and later analyzed by ultrasequencing of the bar-code enrichment). These screenings will allow the creation of a complete map with all the MBF regulators and, by extrapolation, we plan to establish the nodes that regulate the RB pathway (in collaboration with the DeCpario lab at Harvard Medical School).
Required student background: A high motivation towards a scientific career in projects related to basic research, which is the research that is carried out in our group, is a must. Also, a solid background in Genetics, Cell Biology and Molecular Biology is a requirement to carry out this project. Since the project includes bar-code sequencing of pools of KO strains, previous experience with ultra-sequencing will be appreciated. Similarly, previous work with yeast and/or cell cycle will be a plus.

Two-dimensional (2D) monolayers have generated a huge research interest in the past years. The discovery of graphene was awarded with the 2010 Nobel Prize in physics. Very recently, it was realised that twisted bilayer graphene represents a promising platform for understanding the elusive properties of unconventional superconductivity. Better understanding high-temperature superconductors may allow physicists to reach superconductivity at room temperature. This would likely have an enormous impact on our society, since it could dramatically reduce energy consumption in many devices and electricity distribution. Here, we propose to explore new types of twisted bilayer graphene devices in order to understand how superconductivity emerges from the strong correlation between electrons.
When two graphene lattices are overlaid and tilted, they can interfere to create a moiré pattern with a long period. At a small angle of about 1.1º, it was showed that the twisted bilayer graphene stack becomes superconducting. At this “magic” angle, the energy dispersion of electrons becomes flat and the electron-electron interaction parameter becomes large. By tuning the carrier density, the twisted bilayer graphene stack becomes a Mott insulator. These properties are similar to those of cuprates and other high-temperature superconductors. Graphene has two key advantages compared to these materials. First, the band structure of monolayer graphene is simple and well understood. Second, the Fermi energy can be tuned by simply adjusting the voltage applied to the gate electrode in order to characterize the whole phase diagram of electrons. The goal of our research is to fabricate new types of electrical devices based on twisted monolayers in order to understand the physics that leads to superconductivity.

The aim of our research is the development of tools and establishment of methodologies for investigation of the ultrafast events that are caused by electrons inside atoms, molecules, solids and biological matter. The power of attoscience and ultrafast optics lies in the incredible time resolution that gives access to observing the triggering events that are caused by electronic rearrangement and ultimately lead, at hugely varying temporal scales, to molecular dissociation, chemical reactions, excitonic energy transfer or even biological function.
We regularly offer projects within the various research fields and projects of our group.E.g., if you would like to discover extreme nonlinear optics and ultrafast lasers or if you are interested in attosecond dynamics, this is the place to ask! We also have several projects related to numerical simulations, electronic circuit design and data acquisition. You will join our research group and take part in the daily activities, discuss your project, research literature, propose a way to realize some tasks and present your work.The aim of our research is the development of tools and establishment of methodologies for investigation of the ultrafast events that are caused by electrons inside atoms, molecules, solids and biological matter. The power of attoscience and ultrafast optics lies in the incredible time resolution that gives access to observing the triggering events that are caused by electronic rearrangement and ultimately lead, at hugely varying temporal scales, to molecular dissociation, chemical reactions, excitonic energy transfer or even biological function.
We regularly offer projects within the various research fields and projects of our group.E.g., if you would like to discover extreme nonlinear optics and ultrafast lasers or if you are interested in attosecond dynamics, this is the place to ask! We also have several projects related to numerical simulations, electronic circuit design and data acquisition. You will join our research group and take part in the daily activities, discuss your project, research literature, propose a way to realize some tasks and present your work.The aim of our research is the development of tools and establishment of methodologies for investigation of the ultrafast events that are caused by electrons inside atoms, molecules, solids and biological matter. The power of attoscience and ultrafast optics lies in the incredible time resolution that gives access to observing the triggering events that are caused by electronic rearrangement and ultimately lead, at hugely varying temporal scales, to molecular dissociation, chemical reactions, excitonic energy transfer or even biological function.
We regularly offer projects within the various research fields and projects of our group.E.g., if you would like to discover extreme nonlinear optics and ultrafast lasers or if you are interested in attosecond dynamics, this is the place to ask! We also have several projects related to numerical simulations, electronic circuit design and data acquisition. You will join our research group and take part in the daily activities, discuss your project, research literature, propose a way to realize some tasks and present your work.

In our group, we are investigating the mechanisms controlling the reprogramming of somatic cells to pluripotency, and our final goal is to determine if this reprogramming contributes to tissue regeneration in higher vertebrates. In particular, we are studying how the Wnt/beta-catenin signalling pathway and cell-fusion-mediated cellular reprogramming control these processes. We tackle these questions with different approaches and through different disciplines, which range from the nanoscale level of observation of cell functions, up to the whole mouse organ.

This project is linked to a research line whose aim is to understand the health benefits provided by dietary phenolic compounds and the use of nutraceuticals as therapeutic tools in the prevention of cardiovascular and neurodegenerative diseases. In this context, we performed a randomized, double-blind, controlled clinical trial (the PENSA study) that aims to evaluate the efficacy of a personalized multimodal intervention in lifestyle (Mediterranean diet, physical activity, cognitive training and social engagement) combined with the use of epigallocatechin gallate (EGCG) during 12 months, in slowing down cognitive decline in an adult population at risk of developing Alzheimer’s disease (APOE-E4 carriers) exhibiting Subjective Cognitive Decline (SCD).

Although the primary efficacy outcome is change in a composite score of cognitive performance (Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS-PACC), further research is warranted to better understand the biological mechanisms responsible for these effects. Lipidomics is a relatively new emerging discipline with the great potential of elucidating the biochemical mechanisms underlying alterations in lipid metabolism.

The first objective of this project is to study the alterations in lipid metabolism induced by the intervention with Mediterranean Diet. To do so, a targeted lipidomics analysis in plasma samples of participants of the previously mentioned study will be performed. The second objective of this study is to evaluate the correlation between clinical parameters of the study participants and specific lipid species in order to find biomarkers.
The student will have the possibility to actively participate in this research project, to acquire hands-on experience in an analytical laboratory, as well as to be trained on sample preparation and analysis using the state-of-the-art analytical equipment for lipidomics (liquid chromatography coupled to tandem mass spectrometry; LC-MS/MS). Additionally, the student will receive personalized training on how to integrate the results, perform statistical analysis and interpret the obtained data.

We aim to unravel how cells detect and respond to environmental changes. We focus our studies on the characterisation of stress signal transduction pathways, especially those regulated by MAP kinases of the Hog1/p38 family, also known as the stress-activated MAP kinases (SAPKs). Proper adaptation to stress involves the modulation of several basic aspects of cell biology, among them the cell cycle and gene expression. Using S. cerevisiae budding yeast as a model organism, as well as higher eukaryotic cells, we are dissecting the molecular mechanisms underlying cell response to changes in the extracellular environment and characterising the adaptive responses required for cell survival.
Research lines:
– SAPK signalling: Using quantitative data in single cells and mathematical modelling, together with mutational analyses, we study the basic signalling properties of stress-responsive MAP pathways and how to alter them.
– SAPK targets: Using proteomics, biochemistry and genetics, our main goal is to identify new targets for SAPKs and thus widen our understanding of cellular adaptation to stress. This information is expected to facilitate the characterisation of the bases of adaptation in eukaryotes.
– Cell cycle control: SAPKs act in several phases of the cell cycle to allow prompt response to extracellular stimuli and the maintenance of cell integrity. We are uncovering the mechanisms by which Hog1 and p38 SAPKs regulate the cell cycle.
– Regulation of mRNA biogenesis: SAPKs control critical steps of mRNA biogenesis and are thus key regulators of stress-responsive gene expression. Our main aim is to determine the contribution of multiple factors to overall gene expression in response to stress. We are also using genome-wide CRISPR screening to identify essential genes for stress adaptation.

ICFO-Medical Optics group developed techniques based on near-infrared diffuse optics that are being translated to the clinics to measure tissue physiology in neuro-critical care and in oncology. These devices deliver laser light and detect the diffuse photons in order to calculate the laser speckle statistics. These statistics are then analysed by a physical model of photon propagation in tissues to quantify parameters such as microvascular blood flow. In this project, we will test next generation single-photon counting avalanche photo-diodes developed in collaboration with IFAE as highly-sensitive fast detectors. If successful, these detectors will pave the way to next generation novel systems.
The minor project will be at IFAE in design and testing of these detectors.
The expected training outcome is a trans-disciplinary experience in biomedical optics, novel detector technologies and in translational aspects of introducing new technologies to clinical use.ICFO-Medical Optics group developed techniques based on near-infrared diffuse optics that are being translated to the clinics to measure tissue physiology in neuro-critical care and in oncology. These devices deliver laser light and detect the diffuse photons in order to calculate the laser speckle statistics. These statistics are then analysed by a physical model of photon propagation in tissues to quantify parameters such as microvascular blood flow. In this project, we will test next generation single-photon counting avalanche photo-diodes developed in collaboration with IFAE as highly-sensitive fast detectors. If successful, these detectors will pave the way to next generation novel systems.
The minor project will be at IFAE in design and testing of these detectors.
The expected training outcome is a trans-disciplinary experience in biomedical optics, novel detector technologies and in translational aspects of introducing new technologies to clinical use.ICFO-Medical Optics group developed techniques based on near-infrared diffuse optics that are being translated to the clinics to measure tissue physiology in neuro-critical care and in oncology. These devices deliver laser light and detect the diffuse photons in order to calculate the laser speckle statistics. These statistics are then analysed by a physical model of photon propagation in tissues to quantify parameters such as microvascular blood flow. In this project, we will test next generation single-photon counting avalanche photo-diodes developed in collaboration with IFAE as highly-sensitive fast detectors. If successful, these detectors will pave the way to next generation novel systems.
The minor project will be at IFAE in design and testing of these detectors.
The expected training outcome is a trans-disciplinary experience in biomedical optics, novel detector technologies and in translational aspects of introducing new technologies to clinical use.

How does the cerebrovascular reactivity vary over days and weeks? Non-invasive, longitudinal diffuse optical neuro-monitors based on diffuse correlation spectroscopy and near-infrared spectroscopy allow us to study this topic and relate to our findings on pathological conditions (ischemic stroke, traumatic brain injury, carotid stenosis and chronic sleep apnea). This project will study this aspect by measuring healthy volunteers and carry out diffuse optical data analysis, biostatistical analysis and define the healthy variation.

Validation and testing of compact components for diffuse correlation spectroscopy analysis and define the healthy variation.

Diffuse optical instrumentation for translational and clinical biomedical research: develop state-of-the-art biomedical instrumentation for translational and clinical research. These range from portable, hybrid systems that combine diffuse correlation spectroscopy (DCS) with near-infrared diffuse optical spectroscopy (NIRS-DOS) to laser speckle based animal images. We have industrial, biomedical and clinical relationships that drive the specifications of these systems.

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 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 the above mentioned ion channels in heterologous expression systems and neurons from wild-type and disease model knock-in mice. Similar analysis will be performed in fibroblasts of patients and healthy volunteers, and iPSC-derived neurons from those fibroblasts.

The human oral cavity is home to an abundant and diverse microbial community (i.e., the oral microbiome), whose composition and roles in health and disease have been the focus of intense research in recent years. Thanks to developments in sequencing-based approaches, such as 16S ribosomal RNA metabarcoding, whole metagenome shotgun sequencing, or meta-transcriptomics, we now can efficiently explore the diversity and roles of oral microbes, even if unculturable. Recent sequencing-based studies have charted oral ecosystems and how they change due to lifestyle or disease conditions. As studies progress, there is increasing evidence of an important role of the oral microbiome in diverse health conditions, which are not limited to diseases of the oral cavity. This, in turn, opens new avenues for microbiome-based diagnostics and therapeutics that benefit from the easy accessibility of the oral cavity for microbiome monitoring and manipulation. The student will participate in the experimental procedures of several on-going project trying to understand the relationships of the oral microbiota and several diseases, including Alzheimer’s disease, Down Syndrom, and Cystic Fibrosis.
The training outcomes will be: processing of oral samples to profile microbiota, isolation and characterization of microbial species, preparation of DNA and libraries for sequencing, statistical analysis and identifications of significant alterations.

Fungal infections constitute an ever-growing and significant medical problem. Diseases caused by such pathogens range from simple toe nail infections, to life-threatening systemic mycoses in patients with impaired immune systems. The molecular mechanisms driving invasion of mammalian hosts by fungal pathogens poses many scientifically challenging problems, which are as yet little understood. The ability to infect humans has emerged in several lineages throughout the fungal tree of life. Therefore, the problem of elucidating the mechanism for pathogenesis of fungi, as proposed here, can be approached with an evolutionary perspective by detecting specific adaptations in pathogenic lineages. During the last years we have clarified the evolutionary paths to virulence of major fungal pathogens such as Candida glabrata and Candida parapsilosis.

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 the dynamics of membrane contact sites (MCSs), in particular those that form between the endoplasmic reticulum (ER) and the Golgi complex. The Golgi complex is the central organelle responsible of protein transport to various parts of the cell and the post-translational modification of newly synthesized proteins from the ER required for their maturation. It has been recently shown that the membranes of these two organelles come to close apposition to one another forming a dynamic but highly tethered region, termed the MCS. ER-Golgi MCSs facilitate the export of proteins and lipids from the Golgi complex to the cell surface by a still unresolved mechanism. The study of MCS dynamics using conventional microscopy tools has been challenging due to their highly dynamic nature and reduced dimensions. As a result, a clear understanding of the how MCS contribute to transport carrier formation at the Golgi complex is still lacking.

The role of the MSc student will be to perform a set of innovative assays that combine different avant-garde molecular and cell biological techniques, such as the use of fluorescence complementation domains or the retention using selective hooks (RUSH)-system, with state-of-the-art microscopy and nanoscopy tools, such as STED, STORM or intracellular single particle tracking (iSPT). The data obtained will be analyzed using advanced quantitative imaging analysis to finally cast light on ER-Golgi MCS dynamics and their functional relevance for protein secretion.

The objective of the research line on nanoswitches is to develop molecular switches that are regulated with light in order to manipulate and functionally analyze receptors, ion channels and synaptic networks in the brain. These tools are synthetic compounds with a double functionality: They are pharmacologically active, binding specifically to certain proteins and altering their function, and they do so in a light-regulated manner that is built in the same compound usually by means of photoisomerizable azobenzene groups. Recent projects in this area include the development of light-regulated peptide inhibitors of endocytosis named TrafficLights and the synthesis of small molecule photochromic inhibitors to manipulate several G protein-coupled receptors like adenosine A2aR and metabotropic glutamate receptors mGlu5. In addition, some of these light-regulated ligands also bear an additional functionality: a reactive group for covalent conjugation to a target protein. Examples include a photochromic allosteric regulator of the G protein-couple receptor mGlu4 that binds irreversibly to this protein and allows photocontrolling its activity in a mouse model of chronic pain and a targeted covalent photoswitch of the kainate receptor-channel GluK1 that enables photosensitization of degenerated retina in a mouse model of blindness. We also demonstrated for the first time two-photon stimulation of neurons and astrocytes with azobenzene-based photoswitches.
Students can expect to learn the relevant techniques for the proposed project (from synthetic chemistry to electrophysiology and fluorescence imaging, in vitro and in vivo) and to work independently within a team of highly multidisciplinary and motivated researchers.

Protein mediated electron transfer (ET) is essential in many biological processes, like cellular respiration or photosynthesis. The exceptional efficacy of these processes is based on the maximization of donor/acceptor coupling and the optimization of the reorganization energy.
Single molecule techniques can provide physical information on biological processes with molecular resolution and allow the integration of experimental set-ups that reproduce the physiological conditions. They provide information free from averaging over spatial inhomogeneities, thus revealing signatures that are normally obscured by the ensemble average in bulk experiments.
The general goal is to evaluate at the single molecule level the specific conditions that allow for an effective protein-protein ET. We use scanning probe microscopies, SPMs (scanning tunneling and atomic force microscopies and spectroscopies -STM and AFM-), to evaluate immobilized proteins under electrochemical control.
The student will perform studies at the nanoscale using SPMs to measure ET currents and interaction forces between partner proteins, under controlled environmental and biologically relevant conditions (electrochemical potential, temperature, pH, ionic environment). The student will learn to work with SPMs but also on protein immobilization protocols, surface functionalization, electrochemical studies. 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 & Nanoswithces 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.Protein mediated electron transfer (ET) is essential in many biological processes, like cellular respiration or photosynthesis. The exceptional efficacy of these processes is based on the maximization of donor/acceptor coupling and the optimization of the reorganization energy.

Cell processes like endocytosis, membrane resealing, signaling and transcription, involve conformational changes which depend on the chemical composition and the physicochemical properties of the lipid membrane. These properties are directly related to the lateral packing and interactions at the molecular level, that govern the membrane structure and segregation into nano (or micro) domains. The better understanding of the mechanical role of the lipids in cell membrane force-triggered and sensing mechanisms has recently become the focus of attention. The local and dynamic nature of such cell processes requires observations at high spatial resolution. Atomic force microscopy (AFM) is widely used to study the mechanical properties of supported lipid bilayers (SLBs). We investigate the physicochemical and structural properties of lipid membranes combining AFM and force spectroscopy (AFM-FS) under environmentally controlled conditions. We use simplified model membranes including several lipid representatives of mammalian or bacterial cells. We also study the mechanical properties of lipid membranes from nanovesicles with technological applications, like drug delivery.
The general goal is to assess the structure, phase behavior and nanomechanical properties of model membranes, including the presence of glycosphingolipids related to specific pathologies, and associate them to their role processes at the cellular level. 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.

Interested in developing a new gene writing technology? Natural gene transfer is performed by retrotransposons and retrovirus. We are combining precision of modern CRISPR systems with the efficiency of natural gene transfer mechanisms to achieve precise and efficient writing to genomes.

We are offering a master thesis position to develop this technology combining library screening with mammalian directed evolution. This research is funded by an EU H2020 project with top international partners.

Our laboratory is focused on applied synthetic biology for therapeutic purposes. We have two lines of research, one in technology development for gene therapy, and one in skin microbiome engineering. We are located in the PRBB, an exciting international and cutting-edge scientific environment.

Interested in developing novel sensing mechanisms based on natural skin bacteria? Microbes are very sophisticated molecular machines. We have developed methodologies to modify the skin microbiome in humans (Pätzold et al, Microbiome 2019). We are using the skin microbes to expand the functionalities of the host including sensing the environment or the skin status (sebum secretion, immune state). Sensed information can be registered using real time optical reporters or recorded historically on the genome using CRISPR recording.

We are offering a master thesis position to develop sensing genetic circuits to be embedded into the skin microbiome. This research is funded by a US Department of Defense grant and involves very exciting interactions with international partners. Feel free to reach me if you have any question on the project (marc.guell@upf.edu).

Our laboratory is focused on applied synthetic biology for therapeutic purposes. We have two lines of research, one in technology development for gene therapy, and one in skin microbiome engineering. We are located in the PRBB, an exciting international and cutting-edge scientific environment.

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 precised identification genes. The aim of the research project is to develop a gene annotation pipeline 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 (geneid, Guigó et al, 1992), 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 produced full-lengh RNA sequences.
Our pipeline will be based on identifying the genes that can be precisely predicted computationally in a given species, subtract them from RNA samples, and produced high quality RNA sequences for genes that are more difficult to annotate.

The MSc student will join one of the running research projects in the ICFO-QOT. The concrete choice will depend on the current efforts in the group (that change adjusting to scientific needs), student’s preferences and preparation, availability of supervisor/co-supervisor and resources for a specific theme. At this stage ICFO-QOT can absorb one MSc student in this area. QOT-ICFO studies and develops in particular
1) General mathematical theory of quantum correlations, with focus on quantumness, coherence, entanglement and non-locality of states of many body systems.
2) Relations between quantum many body phenomena (quantum phase transitions, quantum criticality, quantum localization, superconductivity, isolating states, topological order and topological phenomena.The MSc student will join one of the running research projects in the ICFO-QOT. The concrete choice will depend on the current efforts in the group (that change adjusting to scientific needs), student’s preferences and preparation, availability of supervisor/co-supervisor and resources for a specific theme. At this stage ICFO-QOT can absorb one MSc student in this area. QOT-ICFO studies and develops in particular
1) General mathematical theory of quantum correlations, with focus on quantumness, coherence, entanglement and non-locality of states of many body systems.
2) Relations between quantum many body phenomena (quantum phase transitions, quantum criticality, quantum localization, superconductivity, isolating states, topological order and topological phenomena.The MSc student will join one of the running research projects in the ICFO-QOT. The concrete choice will depend on the current efforts in the group (that change adjusting to scientific needs), student’s preferences and preparation, availability of supervisor/co-supervisor and resources for a specific theme. At this stage ICFO-QOT can absorb one MSc student in this area. QOT-ICFO studies and develops in particular
1) General mathematical theory of quantum correlations, with focus on quantumness, coherence, entanglement and non-locality of states of many body systems.
2) Relations between quantum many body phenomena (quantum phase transitions, quantum criticality, quantum localization, superconductivity, isolating states, topological order and topological phenomena.

In addition to contributing to finding drivers of cancer and precision medicine, our group is focused on understanding mutational processes by analysing tumour genomes. By studying the observed pattern of somatic mutations across genomic regions, we are able to explore the basic cell mechanisms that produce them. The interplay between these mechanisms, such as internal and external insults that damage DNA, chromosomal replication, transcription, and DNA repair mechanisms, leads to mutational processes that give rise to heterogeneous patterns of somatic mutations across the genome. Our efforts are now focused on generating nucleotide-resolution genome-wide maps of DNA damage and repair upon exposure to chemotherapeutic agents, as we have already optimized a protocol to map alkylation damage in human cell lines.
General objectives:
1. Establish alkylating, UV or crosslinking agent toxicity in selected cell lines
2. Generate nucleotide-resolution maps of DNA damage after treatment
3. Obtain mutation profiles upon DNA damage in wild type and DNA repair-mutant cells
Expected training outcomes:
1. Learn how to culture cells and perform toxicity assays
2. Functional validation of DNA damage: immunofluorescence and comet assay
3. Generate DNA repair deficient mutant cell lines by CRISPR/Cas9
4. Generate a damage library and learn how to interpret the mapping results

The project is dedicated to leverage Machine Learning techniques to new chemical processes that can improve the design of new processes to mitigate CO2 emissions and thus climate change.

This project shall explore the connexion between the COVID-19 propagation and the breast cancer growth based on the mathematics of group theory.
On the one hand, the propagation of the COVID-19 outbreak can be simulated based on complex dynamics’ tools such as a SEIR (Susceptible – Exposed – Infected – Recovered) model which is based on a system of coupled differential equations guiding the pandemic evolution.
While the context is crucial to understand the health data in detail, the dynamics of an averaged group of people can precisely be determined with such models as soon as the virus-dependent epidemiological parameters are known or parameterized.
On the other hand, the development of breast cancer growth, which is, the process leading the cell division, differentiation, movement, organization and death can be parameterized with the principle of minimal energy and a set of dissipative equations. Such equations can be used to explore the conditions for which cancer growth emerges from initial conditions. And again, even though the particular situation will depend on the epistemology of the given cancer, such models can provide accurate dynamics of the tissue growth in simulation.
In both scenarios, apparently disconnected, one can show that the dynamics of the process can be understood from the mathematics of Group Theory thus providing a novel synergy between both fields, an innovative perspective so far unexplored.
In this project, we pretend to establish then the bases for such an enterprise, elaborating first the dictionaries to transfer the dynamics from each field into group theory for later on exploiting what the symmetries found in such processes, which emerge from the group theory exploration, can tell us about mitigation strategies for decelerating their growth.

Our group aims to understand and manipulate electronic, magnetic and optical phenomena at the atomic scale, with the final goal of searching for new ways to sense, and to store and process information. The project proposed here focuses on developing methods to tailor graphene’s properties by nanostructuration.
Graphene is a gapless, diamagnetic semimetal. However, shaping graphene at the nanoscale, doping, and controlling the atomic structure of their edges can lead to magnetism, or to the induction of electronic and optical gaps. We nanostructure graphene by synthesizing 1D nanoribbons on metallic surfaces and fusing them to give rise to a nanoporous membrane. After the synthesis, we explore their singular properties with atomic precision by combining STM with photoelectron and optical spectroscopies. We later transfer them to insulating templates to test their applicability in electronic and optical devices.
The scientific activity of this project is related to the synthesis and characterization of hybrid graphene-based lateral superlattices that can be conceived as quantum platforms for the manipulation of light and spin, or as active layers for photoand electro catalysis. The main objectives are:
– Synthesis of hybrid graphene-based lateral superlattices
– Structural, electronic and optical characterization by scanning tunnelling microscopy and spectroscopy (STM/STS), X-ray photoelectron spectroscopy (XPS), and Raman.
-Transfer to optoelectronic devices for electronic and optical characterizatoin (in collaboration with other team members)
The candidate will be carrying out his own experiments in all task related to the project, always with the help of experienced senior researchers. He/she will gather experience on:
– On-surface self-assembly and chemical methods to synthesize 2D materials
– Scanning tunneling microscopy (STM)
– X-ray photoelectron techniques (XPS)
– Low-energy electron diffraction (LEED)
-Ultra-high vacuum techniques (vacuum components, evaporation of precursors, single crystal preparation…)
Recent related publications of the group:
1. Moreno, C. et al. Bottom-up synthesis of multifunctional nanoporous graphene. Science 360, 199–203 (2018).
2.- Moreno, C. et al. On-surface synthesis of superlattice arrays of ultra-long graphene nanoribbons. Chem. Commun. 54, 9402–9405 (2018).
3.- Panighel, M. et al. Stabilizing Edge Fluorination in Graphene Nanoribbons,.ACS Nano. 14, 11120–11129 (2020).
4.- Li, J. et al., Depopulation of Graphene Nanoribbons Induced by Chemical Gating with Amino Groups. ACS Nano. 14, 1895–1901 (2020).
5.- Moreno, C. et al., Critical Role of Phenyl Substitution and Catalytic Substrate in the Surface-Assisted Polymerization of Dibromobianthracene Derivatives. Chem. Mater. 31, 331–341 (2019).

Alzheimer’s disease (AD) is the most common cause of dementia affecting more than 47 million people worldwide, being a major public health problem with a high economic impact. Due to the progressive increase in life expectancy, it has been proposed that its prevalence will triple in the next 30 years.
EA is characterized by the accumulation of amyloid ß-peptide (Aß) which aggregates into ß-sheets forming neurotoxic oligomers and fibers. The fibers accumulate in the senile plaques of the cerebral parenchyma while the oligomers initiate the damage producing synaptotoxicity that will eventually produce neuronal death. Therefore the production and toxicity of Aß aggregates are determinants in the onset and progression of AD.
There are many experimental evidences that calcium dysregulation is related to the pathophysiology of the disease affecting to synaptic transmission, neuronal death and even increasing Aß production. Our group has recently screened 5,154 mutants of S. cerevisiae that overexpress Aβ, identifying a large number of genes involved in amyloid pathology. Of these we have selected 9 genes that regulate homeostasis and calcium signaling that have not been related to AD at the present time.
HYPOTHESIS: Based on previous studies by our group and other laboratories, we propose the study of the importance of calcium regulation in the pathophysiology of AD by characterizing new genes, not previously related to AD, that play key role in Aß neurotoxicity and production.
OBJECTIVES:
1. Characterization of the new molecular mechanisms mediated by calcium that affect Aß-induced toxicity. The mammalian orthologs of yeast genes that affect Aβ-induced toxicity will be studied in human neuroblastoma cells (SH-SY5Y) and in primary cultures of mouse hippocampal neurons to study their pathophysiological role in neurons. In this study we will focus on the SURF4 protein because of its possible direct relationship with the Ca2 + Store-Operated (SOC).
2. Study of the effect of calcium signaling on Aß production. Characterization of the role of SPCA1 in the production of amyloid through the study of intracellular trafficking of APP, beta- and gamma-secretases and Aß itself.

The kagome lattice, with an in-plane network of corner-sharing triangles made by transition metal atoms provides an exciting platform to study electronic correlations in the presence of geometric frustration and non-trivial band topology. One example that has attracted considerable interest since its discovery in 2020 is the family of metallic kagome compounds AV3Sb5 (A=K,Rb,Cs), which has shown abundant emergent quantum phenomena, including a competition between superconductivity and charge density wave. Their electronic structure is characterized by a Z2 topological invariant and shows multiple van Hove singularities coexisting near the Fermi level. Using state-of-the-art first principles electronic structure methods, this project aims for a deeper understanding of the properties of these materials. We plan to take advantage of the recent implementation of the Bogoliubov-de Gennes theory in the SIESTA package (developed in the Theory & Simulation group at ICN2) to study the superconducting properties of these fascinating compounds.

The goal of this project is to develop a way to understand the electronic structure of mixed-valence coordination polymers (1D-, 2D-, 3D-) using the simple but very useful Marcus-type approach based on first-principles DFT. We shall explore the conductivity of molecular or polymeric organic systems proceeding through a
small polaron hopping type mechanism. In view of the nature of the problem, i.e. the need to estimate the Marcus parabolas associated with the different oxidation states, the use of constrained DFT is needed. This technique has been recently implemented in the SIESTA code, a popular first-principles tool that is under intense development in our group at Bellaterra. The student will get familiarised with state-of-the-art computational tools to simulate the electronic properties of nanostructures, the use of supercomputing facilities, and the basic theory to describe the physics and chemistry of these organic polymers. This project is part of a collaboration with other theorists and leading experimental teams working on oxalate-type Fe(II)Fe(III) 2D networks.

The challenges that are imposed onto our societies by climate change and rising temperatures are recognized internationally as one of the main threats to humankind for the next decades. In short, we reject more than half of the energy produced and consumed globally as heat, into the environment. The same problem persists in the microscale, where devices’s overheating at the microprocessor level compromises computing efficiency, data storage, and network connectivity. Standard approaches to dissipate and recycle heat into useful electricity include thermoelectric coolers and generators, steam engines, air conditioning systems and refrigirators. These are bulky, mechanically complicated, and often inefficient approaches that are based on heat conduction and heat convection. In the thermal photonics group, we are investigating means of controlling and recycling heat via thermal radiation, i.e. using infrared photons. Thermal radiation is emitted by all objects at a non-zero temperature; hence it represents an excellent energy source that we can harness. Recent advances in nanotechnology have allowed the realization of passive radiative cooling schemes where photons emitted at infrared frequencies can cool a macroscopic objects to temperatures below ambient conditions. At the same time, thermophotovoltaic systems that recycle these thermal photons into electricity promise very high efficiencies. In this Master’s project, we will leverage on the properties of emerging materials that are extremely sensitive to their immediate dielectric environment, present very sharp resonant response, and are often highly anisotropic, to control the direction of thermally emitted beams of IR radiation. The project involves analytical and semi-analytical work, numerical simulations, and measurements of thermal emission with Fourier Transform Infrared Spectroscopy.

In our lab, we are studying how epigenetic information is erased during mammalian development. In particular, we study epigenetic reprogramming of the X-chromosome in mouse embryos, induced pluripotent stem cell (iPSC) and in the germ cell lineage in vivo and in vitro. Using a multidisciplinary approach, we want to gain insight into how epigenetic reprogramming is linked to its biological context, with long-term implications for regenerative and reproductive medicine.
In this project, the prospective student would study the function of candidate factors for X-chromosome reactivation in iPSCs and early mouse embryos. The project will involve iPSCs reprogramming and monitoring X-chromosome activity using an XGFP-reporter. Using knockdown and/or CRISPR deletion, the mechanism will be studied, by which the candidate acts on epigenetic reprogramming and at which stage X-reactivation is affected. The student will learn a number of methods including iPSC reprogramming, shRNA knockdown, FACS analysis, immunohistochemistry, RNA-FISH, qPCR, etc.
Besides adding a piece to the X-reactivation puzzle, the student will be immersed within a young team inside a dynamic international research environment at CRG, which will help her/him to gain skills furthering his/her scientific career.

In our lab, we are studying how epigenetic information is erased during mammalian development. In particular, we study epigenetic reprogramming of the X-chromosome in mouse embryos, induced pluripotent stem cell (iPSC) and in the germ cell lineage in vivo and in vitro. Using a multidisciplinary approach, we want to gain insight into how epigenetic reprogramming is linked to its biological context, with long-term implications for regenerative and reproductive medicine.
In this project, the student would work with germ cells from mouse embryos and/or differentiated in vitro from embryonic stem cells (ESCs). The in vitro approach has the advantage of providing more material and being more amenable to perturbation. On the other hand, germ cells from embryos can provide the accurate biological context for testing the applicability of our findings from the in vitro system. Momentarily, we use this two-system strategy to elucidate the signals and mechanisms responsible for X-reactivation in mouse and human germ cells.
Besides adding a piece to the X-reactivation puzzle, the student will be immersed within a young team inside a dynamic international research environment at CRG, which will help her/him to gain skills furthering his/her scientific career.

Without any doubts, the conversion of ubiquitous and typically inert C–H bonds into C–C and C–heteroatom bonds, considered one of the Holy Grails in Chemistry, is one of the most attractive transformations in organic synthesis. Since the second half of the 20th century, the approaches for the cleavage of “unreactive” C–H bonds have evolved from classical electrophilic or radical routes to so-called ligand-directed C–H functionalization protocols. These latter strategies have the potential of simplifying reactions by minimizing the formation of undesired by-products and/or allowing the control of site-selectivity by the use of chelating functional groups present on the reagents. These directing groups (DGs) can bind to the metal center facilitating the reactivity at a specific site on molecules that contain multitude of C–H bonds. Still now, these methodologies predominantly employ precious metals. This has implications for sustainability from both the cost and environmental perspectives.
The Pérez-Temprano group is focused on providing mechanism-driven tailored-made solutions for controlling the chemo- and regioselectivity of directed C–H activation processes catalyzed by cost-effective first-row metal-based systems. By the synergistic cooperation between organometallic and synthetic organic chemistry along with mechanistic studies, we aim to uncover the factors that determine C–H functionalization success or failure to develop more efficient and sustainable chemical transformations relevant for late-stage functionalization, key in medicinal chemistry. In this context, we seek to explore new catalytic systems based on 3d-metals, such as cobalt or manganese for promoting C–C and C–heteroatom bond-forming reactions.

The Biosensors for Bioengineering research group develops multi-tissue organs-on-a-chip (OOC) and integrating sensing technology with tissue engineering. Within this scope, we use in situ biosensors to study insulin release under external stimuli, changes in glucose levels, and myokines secreted by skeletal muscle (multi-OOC approach)1. This project will mimic the complex native muscle structure and organization using precursor cells encapsulated in 3D scaffolds. They support the growth and differentiation of progenitor cells and provide 3D environments to cells. We have developed hybrid biomaterials with tunable mechanical and electrical properties that give structure and support to the cells, and they are biocompatible2,3. This project’s framework will optimize biomaterials to improve other muscle cells’ functionality, longevity, and mechanical and electrical properties. Here we partner with ICFO’s Atomic Quantum Optics group to investigate myotube conductivity using exquisitely sensitive quantum devices known as optically pumped magnetometers (OPMs), which elsewhere are deployed for studies of brain and heart magnetism in vivo, i.e., magnetoencephalography and magnetocardiography4,5.

The project’s main objective is to monitor myotubes’ electrical conductivity and associated magnetic field response. The expectation is for OPMs to allow real-time magnetomyography in the OOC while avoiding invasive electrode placement, unlike direct conductivity measurements6. Tasks: (1) characterize the MMG signal at the myotube level, such as the orientation of the biomagnetic field relative to the cell and temporal response to a single action potential, (2) Identify and characterize responses to chemical stimuli (e.g., drugs), introduced to the OOC.

1. Ortega, M. A. et al. Muscle-on-a-chip with an on-site multiplexed biosensing system for in situ monitoring of secreted IL-6 and TNF-α. Lab Chip 19, 2568–2580 (2019).
2. García-Lizarribar, A. et al. Composite Biomaterials as Long-Lasting Scaffolds for 3D Bioprinting of Highly Aligned Muscle Tissue. Macromol. Biosci. 18, 1800167 (2018).
3. Hernández-Albors, A. et al. Microphysiological sensing platform for an in-situ detection of tissue-secreted cytokines. Biosens. Bioelectron. X 2, 100025 (2019).
4. Knappe, S., Sander, T. & Trahms, L. Optically-Pumped Magnetometers for MEG BT – Magnetoencephalography: From Signals to Dynamic Cortical Networks. in (eds. Supek, S. & Aine, C. J.) 993–999 (Springer Berlin Heidelberg, 2014). doi:10.1007/978-3-642-33045-2_49.
5. Limes, M. E. et al. Portable Magnetometry for Detection of Biomagnetism in Ambient Environments. Phys. Rev. Appl. 14, 11002 (2020).
6. Garcia, M. A. & Baffa, O. Magnetic fields from skeletal muscles: a valuable physiological measurement? Frontiers in Physiology vol. 6 228 (2015).

Which are the most abundant microbial eukaryotic species in the world’s sunlit oceans, and what roles do they play in global marine ecology? Currently, the answers to both these questions remain largely unknown. Microbial eukaryotes (also known as protists) are single-celled and colonial organisms that occupy the size range between bacteria (micrometers) and the smallest multicellular animals (millimeters), a critical position for the function of oceanic food webs. Recent seafaring expeditions, such as the Tara Oceans project, have produced DNA sequence-based catalogs of protists on a global scale. We previously analyzed Tara Oceans data to reveal that only 100 of the approximately 500,000 protist species in the surface ocean make up 50% of total protist abundance. Yet, 92 of these 100 species are unknown to science, and have not even been identified by light microscopy.

The goal of this project is to characterize the biology, interspecies interactions, and ecosystem relevance of these 92 highly abundant, ubiquitous unknown protists. We propose two research and training objectives. First, using a novel isolation approach, we will establish robust laboratory cultures and apply single-cell transcriptome sequencing to produce gene catalogs. Second, we will apply time-lapse light and fluorescence microscopy to understand their life history and behavior and to build hypotheses about their individual and community metabolic potential, followed by laboratory manipulations to test these hypotheses. Overall, we will provide the first glimpse of the morphological, life history, behavioral and transcriptional features of currently unknown globally abundant protists. Discoveries about their biology will have immediate implications for studies of the ecology and community structure of oceanic ecosystems. Finally, we anticipate that our efforts will lead to the establishment of ecologically relevant microbial eukaryotes as new model systems whose biology can be studied intensively in the laboratory.

Molecular mechnisms underlying the phtothermal activity of an antitumoral nanomedicine.

An important part of the group’s work focuses on the stress-activated p38 MAPK signaling pathway, investigating the mechanisms of signal integration by this pathway and its implication in physiological and pathological processes. Our results have provided in vivo evidence for the implication of p38 MAPKs in homeostatic functions, beyond the stress response, and have illustrated how dysregulation of this pathway may contribute to cancer and other diseases. Recently, we have demonstrated key roles for p38 MAPK signaling in tumor progression as well as in the resistance to chemotherapeutic drugs using mouse models. Our work combines studies using genetically modified mice and chemical inhibitors, with experiments in cancer cell lines and biochemical approaches. An important aim of our work is the identification of therapeutic opportunities based on the modulation of p38 MAPK signaling. Ongoing projects in the group address two main topics: (1) Cancer cell homeostasis and chemoresistance mechanisms, and (2) Cross talk between cancer cells and stromal cells.

Our group applies single-cell and clonal analysis technologies to provide a more unbiased understanding of cellular physiology and disease. We combine single-cell sequencing with lineage tracing to understand how gene expression dynamics in stem cells (variation) contributes to distinct cellular functions. There are two Master’s thesis projects available, both focused on developing new technologies for studying stem cell dynamics in the hematopoietic system:
1. A method for combining gene perturbations with lineage tracing to study the molecular machineries that regulate differentiation rates/dynamics.
2. A quantitative method for recording inflammatory perturbations that can be sequenced in typical single-cell assays.

We are interested in using machine learning methodologies to analyze mutation patterns in cancer genomes, in order to (a) learn about mutagenesis and DNA repair mechanisms in human, and (b) predict cancer evolution such as the appearance of drug resistance mutations. The student will learn genomic data analyses methods (bioinformatics and statistical genomics), cancer biology,, applied machine learning and data visualization.

In recent years, ultra-cold atomic gases have emerged as a novel platform for the study of quantum many-body systems. They provide quantum matter that can be controlled almost at will using the tools of optics and atomic physics, and allows one to engineer a very broad range of model Hamiltonians in a single table-top experiment. This bottom-up approach comes very close to Feynman’s idea of a “quantum simulator” – a special purpose quantum computer that can solve problems currently out of reach for classical machines – and, besides enabling the study of long-standing physics questions, also gives access to completely new forms of quantum matter. In our group, we have two quantum gas laboratories that focus on complementary aspects of quantum gas research.

In the potassium lab, we investigate mixtures of quantum gases where the competition of interactions with different origins reveals the subtle effects of quantum fluctuations and stabilizes new phases. For instance, we exploit mixtures of Bose-Einstein condensates (BECs) to create the most dilute liquids existing in Nature, and use them to understand better the role of quantum correlations in quantum many-body physics [C. R. Cabrera et al., Science 359, 301 (2018)]. Using lasers that couple two internal states of the atoms, we also engineer collective many-body states which are described by topological gauge theories originally proposed in the context of fractional quantum Hall physics, and investigate their chiral properties. Finally, in ongoing experiments we are trying to create a supersolid liquid: a phase which exhibits simultaneously the phase coherence of a superfluid, the crystalline structure of a solid, and forms self-bound droplets like a liquid.

In the strontium lab, we aim at synthesizing the cleanest and purest “solids”. To this end, we will trap quantum degenerate fermionic atoms in optical lattices – artificial crystals of light created by interfering laser beams – and probe their properties by detecting every single atom and lattice site using fluorescence imaging. With such quantum gas microscope, we want to perform quantum simulations of the Fermi-Hubbard model [L. Tarruell and L. Sanchez-Palencia, C. R. Physique 19, 365 (2018)], which is believed to hold the key of high-temperature superconductivity. Moreover, because strontium has 10 internal states, we can extend our studies to “electrons” of spin larger than 1/2, for which completely new types of quantum magnets are expected. The strontium apparatus is currently under development. Our experiment already produces laser-cooled fermionic atoms at microkelvin temperatures, and we are currently developing the quantum gas microscope part of the setup.

We offer Master theses on the two laboratories. They will focus on the development of an experimental subsection of the apparatus, and will include a small theoretical part focusing on its design, and a larger experimental part consisting on its construction and characterization. Several projects are possible depending on the skills and interests of the candidates, and on the advancement of the experiments. For further information, references and a list of former Bachelor and Master projects completed in the group, please consult www.qge.icfo.es

We are looking for candidates with a good background in quantum optics, atomic physics or condensed-matter physics, and a strong motivation for setting up and conducting challenging experiments in a team of three to four people. We offer training in a broad range of cutting-edge experimental techniques (from optics, electronics, ultra-high vacuum technology and computer control to quantum state engineering), as well as in theoretical atomic, quantum, statistical, and condensed matter physics.

In this project you will work with state-of-the-art ultrafast laser systems, in order to study optical, electrical and, especially, thermal phenomena in novel quantum materials. You will get hands-on experience with the fabrication of samples based on 2D materials with a thickness down to the atomic monolayer, and will learn how to study these exciting material systems with advanced optoelectronic setups with femtosecond time resolution.

Semiconductor detectors are being increasingly used in medical applications and, in general, as imaging systems. The IFAE Medical Physics group is developing a new generation of silicon devices for radiation detection that is based on the commercial CMOS technology. The devices are designed to be sensitive to infrared radiation (IR) for usage in neuromonitoring systems (brain blood flow measurements). In the course of this program, the selected candidate will work on the development of a system to operate these novel avalanche photo-didoes, carry out their characterization in the IFAE laboratory and test them at ICFO on tissue simulating phantoms.

Intrinsically disordered proteins (IDPs) retains a large portion of flexibility that allows proteins to sample a large conformational space. Therefore, IDPs are excellent binding partners that are able to interact with a plethora of cellular components and are involved in many signaling and cell regulation events (Eftekharzadeh et al., 2019 Nat Comm.; De Mol et al., 2018 Structure). Given their increased accessibility and exposed surface, they are also tightly regulated by post-translational modifications and protein processing. Conversely, it is generally thought that the lack of a well-defined structure impedes the structure-based rationalization of small-molecules drugs, although several original approaches are being explored (Fuertes et al., 2019; Heller et al., 2020). Recently, IDPs have been reported to be involved in the formation of membrane-less organelles by phase separation (Bouchard et al. 2018 Mol. Cell). An ambitious goal of our research group is to decipher the molecular basis that regulate the phase separation propensities of IDPs and set the basis for the development of drugs that modulate their properties. To this end, novel approaches, both technical and conceptual, are under development in our group. The proposed project for a prospective master student contains (i) the biophysical characterization of an IDP liquid-liquid phase separation, (ii) the atomic-resolution study of IDP-drug interactions by nuclear magnetic resonance, and (iii) the participation in a multidisciplinary environment (from biophysics to cell biology) that aims to make a substantial contribution in the drug discovery of challenging cancer targets.

Our lab studies the interplay between genetic mutations and pro-inflammatory tissue signals that promotes cancer development, with a focus on pancreatic and liver cancers, two clinical challenges in dire need for early detection and interception strategies. As cancer pathogenesis hijacks processes that can be key to safeguard normal tissue homeostasis (eg wound healing), we combine bulk/single-cell epigenomic profiling and flexible disease models to uncover the molecular and cellular traits that are unique to tissues undergoing neoplastic transformation, and apply functional genomics tools (RNAi/CRISPR) to pinpoint the key mechanisms responsible for disease progression.

The available Master projects will focus on developing new tools for capturing and perturbing molecular programs and cellular states that are induced by the cooperative action of oncogenic mutations and inflammation during cancer development (Alonso-Curbelo et al. Nature 2021):

1. Genetic tagging of tumor cells with unique capacities to drive and/or sense inflammation.
2. Functional dissection of molecular programs distinguishing pancreatic tumorigenesis and normal regeneration.
3. Computational mining of early tumor-specific markers in bulk and single-cell sequencing datasets.

Through this opportunity, the student will acquire training on general cancer biology, molecular cloning, functional validation approaches (RNAi/CRISPR-mediated genetic perturbations), histology (immunofluorescence/immunohistochemistry), flow cytometry, culture of pancreatic organoids and cell lines, and experimental design, data analysis and reporting. The student will also work with our team to set-up experimental pipelines in our newly opened lab and contribute to a constructive and stimulating working environment.

Keywords: Cancer, inflammation, epigenetics, pancreatic cancer models, CRISPR/Cas9

The proposed project will develop non-invasive assays based on magnetic resonance (MR) to study glucose metabolism and further the understanding of metabolic diseases such as cancer, non-alcoholic fatty liver disease and muscle dystrophy, aiming to provide a platform for personalized drug testing on organ-on-a-chip systems.
We use hyperpolarized 13C magnetic resonance imaging (MRI) and spectroscopy (MRS), where signals from endogenous molecules are detected with chemical specificity. This technique allows us to detect the chemical reaction kinetics of an individual metabolic pathway in real-time, in vivo and in a non-invasive manner. Hyperpolarized 13C MRI/MRS has been used to study metabolism in cells, in vivo in animals and it is already transitioning into phase I clinical trials (both in the USA and Europe). In our group, we aim to bring this technique to detect real-time metabolism in organ-in-chips, working on methodology for hyperpolarized 13C MR and organ-in-chip devices as well as identifying new biomarkers and potential MR probes of abnormal cell metabolism and biochemical pathways.

The molecular mechanisms driving aging are embedded within complex physiologic networks. At long time-scales, these mechanisms exhibit emergent, collective behaviour that is both a fascinating topic and a fundamental barrier for traditional experimental approaches to establish molecular-level causality.  To understand biological aging and develop effective therapies against it, we need better and more quantitative approaches that can rapidly characterize the multiple, complex causal pathways through which molecular-level changes determine systems-level dynamics.

The Dynamics of Living Systems group is an interdisciplinary team that pursues these goals through a mix of molecular genetics, synthetic biology, high-throughput imaging, machine learning, modelling, and math.

We are currently looking for two candidate profiles:

1.     Candidates with an interest in developing and applying data science approaches to analyze multi-omic, time-series data.

2.     Candidates with an interest in primarily theoretic projects, aimed at understanding causality, interdependency, and stochastic phenomena in complex
networks.

The phenomenon of CP violation relates to another mystery in our understanding of the universe. If the Big Bang created matter and antimatter in equal parts, why is the universe composed of matter? In 1967 Andrei Sakharov proposed three conditions to produce an excess of matter in the early universe, and one of these is the presence of CP violation. However, it was ultimately found that the CP violation in the quarks and hadrons, such as the neutral kaons, was not sufficient to explain the imbalance in our universe. Hence, we look for new sources of CP violation, and one candidate is the phenomenon of oscillations neutrinos.
Hyper-Kamiokande (Hyper-K) is a next generation underground water Cherenkov detector, based on the highly successful Super-Kamiokande (Super-K) experiment. It will serve as a far detector of a long baseline neutrino experiment for the Japan Accelerator Research Comlex (J-PARC) neutrino beam, with the main focus on the determination of CP violation, and will also be a detector capable of observing – far beyond the sensitivity of the Super-K detector – proton decay, atmospheric neutrinos, and neutrinos from astronomical sources.
In CP violation measurements at Hyper-K, it is important to disentangle electrons from pi0 and identify weak rings from charged pions in final state topologies in order to retain events which are useful for the extraction of the CP violation phase. This separation and identification will be improved in this project with modern techniques of Machine Learning (ML), namely neural density estimators and convolutional neural networks (CNNs).
The expectation is to achieve a reduction of a factor 4 in electron/pion0/muon/charged pion reconstruction inefficiency using ML methods. The strategy could be applied in determining CP violation parameters with a nu_mu beam in the Hyper-K detector.

The alarming increase of CO2 levels, due to anthropogenic and industrial activities, has become a serious environmental issue nowadays. A plausible solution to minimize the negative impact of CO2 emissions is to develop carbon-neutral approaches, i.e., reduction of CO2 into valuable compounds. This research project deals with the development of efficient photocatalytic systems for the gas-phase conversion of CO2 in the presence of water under sun-like irradiation and dark cycles. The main goal is to fabricate supported photocatalysts with one-dimensional (1D) heterostructures for enhancing light harvesting and electron mobility properties, which will result in higher photocatalytic performances than those obtained with bulk semiconductors. Moreover, the decoration of these photocatalytic systems with quantum dots and luminescent materials will provide them with advanced light conversion abilities, e.g., NIR-light response and light energy storage/release. Such new features will be crucial not only to promote their photoactivation in the full range of the solar spectrum (UV-vis, near-infrared) but also to maintain their photoactivity under intermittent light/dark cycles in a similar way to natural photosynthetic systems

In this project, we will develop assays that recapitulate the functions of SARS-CoV-2 proteins under standard safety laboratory conditions. We will focus on the Spike protein which mediate virus entry into cells and on viral proteins that suppress the innate immune response. Using genome-wide CRISPR screens, we will identify host proteins that promote or inhibit the function of these viral proteins. We will then determine the molecular mechanisms that mediate these interactions using biochemistry and cell biology approaches.The results of this project will provide insights into the mechanistic basis of SARS-CoV-2 pathogenesis and may identify targets for anti-viral therapies.

Cancer-associated cachexia is a nutritional wasting disorder with no effective treatment that is often fatal—up to 30% of patients who die of “cancer” in fact succumb to cachexia. Surprisingly little is known about the mechanisms underlying it, hindering any therapeutic advances. We now propose that cachexia stems from metastastic-inducing cancer cells that have “hijacked” the body’s tissue repair system, leading to energy being drained from the body and going into the metastatic cancer progression/growth. This project stems from previous work in our lab where we have identified and characterized metastatic cells in many tumor types (Nature 2021; Nature 2017; Nat Cell Biol 2018; Nat Metabolism 2020; Elife 2017). To understand this in molecular detail, we will use state-of-art technologies to examine mouse models in vivo and mouse and patient-derived cells in vitro. We aim to determine the specific molecular pathways that led to cachexia, and whether re-routed cells have a defined pro-cachexia signature. Overall, we expect to reveal actionable targets for future therapies (via drugs, diet supplements, etc), with the potential to improve quality of life and survival for patients with cancer.

The direct detection of gravitational waves was one of the most important milestones in Physics of recent years, as recognized by the Nobel prize of 2017. It has allowed us to explore new phenomena of the Universe, verify the existence of black holes, and confirm some of the most spectacular predictions of Einstein’s theory of general relativity. Still, an aspect of gravitational waves has remained elusive to verification. Indeed, all other interactions of Nature are quantized, a property expected also for gravity, yet not confirmed. Quite interestingly, the current developments in the precision frontier, e.g. in quantum technologies, may change this situation, and allow us to access the first hints of the quantization of gravitational radiation. In this project, we will characterize under which situations the quantum nature of gravitational waves may be relevant and how to access this regime with current or future detectors. The latter will be based on state-of-the-art technologies, as atom or light interferometers, atomic clocks, etc. The result of this project will provide insights into some of the most fundamental aspect of gravitation yet to be proven, and also will give the student the tools to continue her/his work on the frontier of fundamental physics and quantum devices.

The Nanobioengineering group at IBEC is a multidisciplinary team applying nanotechnology for the development of new biomedical systems and devices, mainly for diagnostic purposes, and integrated microfluidic Organ-on-Chip devices for the study of organ physiology, disease etiology, or drug screening. The group uses nanotechnology applied to biomolecule interaction studies and micro/nano-environments for regenerative medicine applications. Particularly, we work on the development of bioengineered 2D and 3D micro/nanoenvironments with a topography and chemical composition controlled at the nanoscale for cell behavior studies (adhesion, proliferation, differentiation) and the biophysical description of cellular phenomena (cell migration, differentiation) using micro/nanotechnologies, cell biology tools and soft matter physics.
The proposed project aims at Deciphering key cell-matrix interactions in differentiation and disease of the musculoskeletal system tissues.
Cell environment is an essential regulator in development and in tissue functioning. This regulation is exerted hierarchically from the nanoscale with impact at the macroscopic levels.
Transmission of matrix information to cells and inside the tissue occurs at the cell membrane. There, nanoclusters of membrane receptors are formed as a compartmentalization ubiquitous strategy for signal transduction. At the Nanobioengineering group we are interested in the development of molecular tools that aid at deciphering the cell-matrix interactions at the nanoscale and their impact in tissue formation and disease.
The current project aims at recapitulating the extracellular matrix (ECM) characteristics at molecular, nano and meso levels that determine cell behavior. Applications will be focused on cell differentiation and disease-related active ECM remodeling involving the musculoskeletal system and with impact in regenerative medicine. To reach this goal, the student will familiarize with the chemical and biological tools currently used in the laboratory such as nanopatterning and extracellular matrix production, surface characterization techniques, cell culture, live imaging, and data processing to address the mechanical and chemical events driving cell-matrix interactions. During the thesis project, the student will learn how to work in a multidisciplinary and dynamic environment. He/she will develop tasks involving advanced technologies in bioengineering, nanotechnology, cell biology, microscopy, image processing and mechanobiology.

The proposed project would consist in the continuation of a study on the antibody-mediated Natural Killer (NK) Cell response to Epstein Barr virus (EBV) (López-Montañés, Alari-Pahissa et al. JImmunol 2017; Alari-Pahissa et al. PlosPathogens 2021). EBV causes a highly prevalent and lifelong infection contributing to the development of some malignancies. When NK cells recognize, through the Fc receptor (CD16), antibodies (Abs) bound to EBV-antigens in the membrane of infected B cells, they become activated, produce TNFa and IFNg and release cytotoxic granules containing perforin which kills the infected B cell. We previously reported that when viral particles are attached to the B cell surface prior to infection, NK cells may be also activated by EBV-bound Abs producing TNFa but not IFNg, and releasing cytotoxic granules that, remarkably, do not result in B cell death. Recently, we showed that in this setting , NK cells may partially inhibit B cell infection, uptaking the viral particles and internalizing them through a trogocytosis-like process. We intend to investigate on one hand why the viral particle-coated B cell is not killed in spite of NK cell degranulation and, on the other hand, whether activation under these conditions may result in NK cell exhaustion. In relation to the first objective, we hypothesize that when the antigen is on the viral particle attached to the B cell, the indirect NK-B cell interaction is insufficient to promote synapse formation required to efficiently trigger effector functions. It has been recently shown that cytotoxic cells pull the membrane of target cells increasing the membrane tension, and that this makes the insertion of perforin more efficient.The project would involve the realization of molecular biology, transfection, flow cytometry, microscopy and video microscopy techniques. The main experimental line would consist in generating transfectants of viral antigens in a B cell line and comparing them with the same cell line coated with VP in the way they interact with NK cells through anti-EBV Abs in flow cytometry, microscopy and video microscopy experiments, measuring frequency and duration of synapses as well as membrane tension.

This project is linked to a research line whose aim is to understand the health benefits provided by dietary phenolic compounds and the use of nutraceuticals as therapeutic tools in the prevention of cardiovascular and neurodegenerative diseases. In this context, we performed a randomized, double-blind, controlled clinical trial (the PENSA study) that aims to evaluate the efficacy of a personalized multimodal intervention in lifestyle (Mediterranean diet, physical activity, cognitive training and social engagement) combined with the use of epigallocatechin gallate (EGCG) during 12 months, in slowing down cognitive decline in an adult population at risk of developing Alzheimer’s disease (APOE-E4 carriers) exhibiting Subjective Cognitive Decline (SCD).

Although the primary efficacy outcome is change in a composite score of cognitive performance (Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS-PACC), further research is warranted to better understand the biological mechanisms responsible for these effects. Lipidomics is a relatively new emerging discipline with the great potential of elucidating the biochemical mechanisms underlying alterations in lipid metabolism.

The first objective of this project is to study the alterations in lipid metabolism induced by the intervention with Mediterranean Diet. To do so, a targeted lipidomics analysis in plasma samples of participants of the previously mentioned study will be performed. The second objective of this study is to evaluate the correlation between clinical parameters of the study participants and specific lipid species in order to find biomarkers.
The student will have the possibility to actively participate in this research project, to acquire hands-on experience in an analytical laboratory, as well as to be trained on sample preparation and analysis using the state-of-the-art analytical equipment for lipidomics (liquid chromatography coupled to tandem mass spectrometry; LC-MS/MS). Additionally, the student will receive personalized training on how to integrate the results, perform statistical analysis and interpret the obtained data.

CO2 capture and conversion using renewable energy stands out as one promising strategy to revert global warming. CO2 electroreduction (CO2R), in particular, enables the transformation of CO2 into widely used chemicals that could be readily used in our society as fuels and chemicals.
CO2R requires high product selectivity (among the different oxo-hydrocarbons that could be produced), high productivity or local density, high energy efficiency, and high stability. This pursued by the design of catalysts that, from the atomic level, interact with CO2, water, ions and electrons in ways that promote a given reaction pathway.
The prospective student will:
– Dive into the field of CO2 capture and conversion;
– Design and fabricate CO2R catalysts tailored to a specific reaction;
– Characterize the materials and the reactions using a combination of different advanced operando spectroscopies;
– Implement the resulting catalysts into electrolyzer reactors and characterize their performance.

Suggested literature:
10.1126/science.aav3506
https://doi.org/10.1039/D0EE02981E

The discovery of new materials has fueled the most relevant technological advances across history. Advances in modern chemistry and physics, combined with nanotechnology have enabled a rapid growth in the knowledge and utilization of emerging materials, offering guidance into their design from the atomic level, synthesis, and discovery of new classes of materials.

There are virtually infinite combinations of materials in terms of composition and structure. To date, the discovery of new materials has been based on serendipity, empirical observations, or time-consuming computational modeling. In this project, we will utilize artificial intelligence to accelerate the design of new materials for energy harvesting and storage applications.

The prospective student will combine work on some of the next:
– Coding, data science, analysis, and artificial intelligence
– Computation modelling of materials
– Mechatronics, automation of synthesis and characterization
– Self-driven laboratories

Suggested literature:
https://www.nature.com/articles/s41578-018-0005-z

“Our group studies the interactions between light and the quantized states of electrons in atoms. The electronic states of alkali atoms, in
particular, can be extremely sensitive to magnetic fields, where fields down to 10^(-15) tesla can be detected.  This high sensitivity enables atom-based magnetometers to make an impact in healthcare – such as imaging neural currents inside the brain, or detecting arrythmic activity of fetal hearts – and other sectors including navigation and timekeeping.

Our lab develops new ways to improve atomic magnetometer performance, as well as new applications: https://www.youtube.com/watch?v=CZZrfKs2VfI

Projects are available in the following areas:(1) We use microfabricated atomic cells, targeted at wearable devices for the healthcare sector; (2) We “quantum enhancement” approaches, such as polarization squeezing, that have the potential to surpass standard quantum noise limits in magnetometers; (3) We apply optimal signal-tracking approaches, such as a Kalman filtering, to magnetometry (4) We apply magnetometers to detect magnetic activity of biological systems, e,g, muscle (5) We apply magnetometers as sensors for magnetic resonance imaging (MRI) of soft matter (6) We investigate techniques to transfer alkali atoms polarization to nuclear spin species in inert gases (e.g. 129Xe, N2, 3He), for use in gas-phase imaging applications

The student will have the opportunity to learn about cutting-edge devices in quantum sensing and magnetometry within the environment of an international research team. The project will be experimentally  focused, allowing the student to address a scientific question. Some fluency in programming is required (C/C++, python, Matlab or Mathematica) for data analysis and to perform simulations of the experiment on a computer.

Please see the group webpage for recent publications: https://mitchellgroup.icfo.es/mg/pmwiki.php

Despite tremendous progress in therapeutic drug development, more than 80% of all human proteins remain beyond the reach of inhibitor-centric traditional drug discovery, including some of the most prolific cancer targets.
Targeted protein degradation (TPD) is based on small-molecule drugs, generally called “degraders”, which induce proximity between a ubiquitin E3 ligase and a target protein of interest. As a result, the target protein is ubiquitinated and then degraded by the proteasome. Overall, the TPD technology represents a novel paradigm in drug discovery that holds the promise to eliminate otherwise undruggable proteins.
Having TPD as a foundational basis, our lab pursues highly interdisciplinary biomedical research that ranges from drug hunting to elucidation of exciting molecular biology. In brief, we develop screening strategies to find degrader compounds with therapeutic interest, and we tackle biological questions that benefit from the high kinetic resolution of TPD or that involve E3 plasticity dysregulation.
The global goal of this master project is to guide the innovation of next-generation anti-cancer therapeutics. Specifically:
1. To innovate drug screenings aiming to find degraders with therapeutic value in cancer.
2. To elucidate the mechanism of action of novel degraders and the phenotypic consequences at a single-cell level resolution.
Chemogenetics, proteomics, CRISPR screens or drug pulldowns are among the approaches that will be learnt.

Cancer is a multi-hit process involving mutations in oncogenes and tumor suppressors, as well as interactions between the tumor cells and the surrounding stroma. Cancer as a disease is characterized by a series of hallmarks, which include sustained proliferative signalling, resistance to growth suppressors and to cell death, increased replicative immortality, invasiveness and metastasis, energy metabolism reprogramming, genome instability, and inflammation. We are interested in the cellular and molecular mechanisms underlying the regulation of many of these hallmarks, especially the role of Genome Instability in tumourigenesis.

The fruit fly, Drosophila, is an excellent, genetically-tractable system for modelling the development of cancer, due to the conservation of signaling pathways, cell proliferation and survival genes between fly and humans, its suitability for genetic and molecular manipulations, and its well-described developmental biology. Working with flies (an in vivo approach) allows the analysis of tumours at the cell autonomous level but also at the systemic level (relationship between tumours and the rest of the body). Drosophila is also useful to perform high-throughput screening of small molecule inhibitors that can be developed to combat human cancer.

The human body contains 2–3 g of zinc.Deficiency in zinc causes impairment in body growth, neurological disorders and immunosuppression, leading to morbidity and an increased infection rate. In this context, our group has recently published an observational study showing that COVID-19 patients with lower plasma zinc content have worse prognosis, increased time of hospitalization and mortality. The general goal of the project is to better understand the potential benefits of using zinc as a nutriceutic in infectious diseases. The specific objectives are: i) to characterize the impact of zinc supplementation in the immune system and ii) to study at the cellular level the signalling pathways implicated in this regulation.The project is based on a multidisciplinary approach combining immunology and biophysics. The students will acquire skills in different techniques of both disciplines.