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

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.

This master thesis will focus on the automated synthesis of solution processed materials that have potential for energy and information technology applications such as perovskites and sol-gels. The candidate will lead or contribute to the following: 1) using robotized platforms, program the synthesis of perovskite and sol-gel-based materials; 2) automate the analysis of their resulting materials, including structure and composition; 3) automate the analysis of the materials properties (e.g., bandgap, complex permittivity, carrier density/mobility) related to a target application (e.g., energy storage, energy harvesting, information storage and processing); 4) implement models that, using these information, design the next experimental step, ultimately enabling the realization of self-driving unsupervised laboratories.

Depending on the candidate’s expertise and interests, the project will be designed to contribute to a subset of the above.

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.

Stacks of twisted bilayer graphene have been shown to possess superconducting, correlated insulating, and magnetic states coexisting in devices with the magic angle of 1.1 degree. Superconductivity and a correlated insulating phase at first sight appear to be related, suggesting electron-electron interaction as the driving force behind superconductivity, but its nature remains elusive. Magic angle twisted bilayer graphene (MATBG) thus proves to be a powerful platform to study these phases, however the underlying mechanics that rely on have yet to be explained. To this end, this PhD project aims to exploit additional degrees of freedom offered by suspending MATBG. In these MATBG electromechanical devices, electrostatic gating will enable strain-dependent studies of these novel phases. We will also explore the coupling of these phases with mechanical vibrations. This project will take place at ICFO. Our group has strong expertise in the fabrication of MATBG devices, and their electrical characterization in the sub-Kelvin range. The tasks of the student will be the fabrication of these devices and their measurements in dilution cryostats.

Touch-based social learning in C. elegans.

We are looking for a master student to study the role of gentle touch during development of C elegans for establishing social interactions during aggregation behavior. The successful applicant will learn advanced genetic technique to manipulate the ability to sense mechanical touch at different stages of animal development and investigate the consequence on social aggregation behavior using time lapse video recordings. Tools to manipulate touch sensation in a spatiotemporal manner are already established in the NMSB lab and ready to be applied. In the second stage of the project, the applicant will work with a PhD stundent to visualizze and quantify whole brain calcium dynamics on an open top light sheet microscope under mechanical stimulation. The final goal is to trace the circuit for gentle-touch based social learning and the molecular underpinnings in a genetic model organism.

The molecular mechanisms driving aging are embedded in 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:
• Students interested in wet-lab experiments, with a masters degree in genetics, genomics, biomedical engineering, or molecular biology
• Students interested in computational work, with a masters in engineering statistics, physics, computer science or bioinformatics

Chromosomal Instability (CIN), defined as an increased rate of changes in chromosome structure and number, is a feature of most solid tumours. While CIN is shown in certain cancers to contribute to sculpt the genome of the tumour cell by promoting the gain of oncogene-carrying chromosomes and the loss of tumour-suppressor-gene-carrying chromosomes, the impact of CIN on the biology of the cell and on the homeostasis of the tissue, as well as the role of CIN in tumorigenesis are far from being completely elucidated. Our lab has recently developed an epithelial model of CIN-induced tumorigenesis in Drosophila that has led to the identification of emerging, tumour-like, cellular behaviours such as epithelial to mesenchymal (EMT)-like cell fate transitions, cell invasiveness and metastatic behaviour, senescence, unlimited growth potential and malignancy. The Master student will contribute to characterize the molecular mechanisms mediating these cellular behaviours.

The accelerated expansion of the Universe, discovered in 1998, and the need for a new force behind this acceleration, called Dark Energy, is still one of the most mysterious findings in cosmology. In order to understand the nature of this force, the European Space Agency will launch the Euclid satellite mission in 2023. By mapping the Universe, Euclid will not only be able to shed light on the nature of dark energy, but also to measure the neutrino mass, test General Relativity at cosmological scales and to study the inflationary phase at the first 10^{-30} seconds of the Universe.
For that, Euclid will map the 3D position of millions of galaxies and study their clustering statistics. For instance, studying the 2-point correlation function: how the density of galaxies is correlated over two different regions of space given the distance between them. For that, Euclid relies on measuring their infrared spectra and identifying H-alpha emission lines. However, a fraction of the observed lines will be OIII miss-identified as H-alpha, resulting in obtaining the wrong position for those galaxies. Understanding carefully this effect on the observed clustering is a key factor for the success of Euclid.
The student will work with Euclid simulations to quantify the impact of the line miss-identification on galaxy clustering statistics. They may also explore how to model this effect in order to recover unbiased cosmological results. The student will have access to High Performance Computing facilities to analyze the large amount of simulated data provided by Euclid. The analysis skills trained in this endeavor are easily transferable to other Bigdata projects.
The host group was involved in the construction of parts of the satellite and is also heavily involved in the analysis of different galaxy survey international collaborations. Hence, this is the perfect environment for this research project.

The European Space Agency will launch the Euclid satellite in 2023. One of the main goals is to better understand the physics of the first 10^{-30} seconds of the Universe, when inflation took place. During this phase, the Universe expanded exponentially and the seeds of the Large-Scale Structure (LSS) of the Universe were created by inflating tiny quantum fluctuations to extragalactic scales. This created patterns, which we can observe today in the distribution of galaxies in the Universe. The simplest models of inflation predict a pristine Gaussian distribution of these initial conditions, however, more exotic models predict Primordial Non-Gaussianities (PNG). For that, Euclid will map the position of millions of galaxies and study their clustering statistics, mainly with the 2-point correlation function: how the density of galaxies is correlated over two different regions of space given the distance between them. In the presence of PNG, there should be a characteristic increase of signal at very large scales. This is a unique opportunity to shed light on this primordial epoch of the Universe.

It was recently proposed that selecting galaxies according to their environment would greatly increase the chances to detect PNG (Castorina, arxiv:1803.11539). This was, however, never tested in realistic PNG simulations. The group at IFAE has recently created the largest PNG cosmological simulations to date, thus being in a unique position to test this hypothesis.

The student will construct different Euclid-like galaxy samples in the PNG simulations to test the hypothesis of Castorina. They will also analyze the clustering statistics of these galaxy samples in order to detect the PNG signal. They will have access to High Performance Computing facilities and the analysis skills trained in this endeavor are easily transferable to other Bigdata projects. The host group was involved in the construction of parts of the satellite, is also heavily involved in the analysis of different galaxy survey international collaborations and led the PNG simulation project.

The host lab is interested in addressing several questions such as: how does the sequential production of the diverse neurons occur; what is the relative contribution of distinct progenitor cell pools to specific fu¬nctional circuits? and which are the Gene Regulatory Networks (GRN) operating in the transition from stem cell progenitors to differentiated neurons. Recently, we have assessed the contribution of the different proneural genes (PN: neurog1, ptf1a, ascl1b) expressing progenitor pools to glutamatergic and GABAergic neuronal populations, by progenitor-restricted intersectional fate mapping. Next, we will generate a temporal neuronal differentiation map of the different PN-progenitor derivatives.

In this project, the candidate will be involved in dissecting the specific transcriptional signature of glutamatergic and GABAergic neurons deriving from neurog1, ascl1b and ptf1a progenitor pools. Zebrafish hindbrains will be used to FACS-sort neurons deriving from different progenitor pools and cells will be transcriptionally profiled by scRNA-seq. These results will provide the specific transcriptional signature of glutamatergic and GABAergic neurons deriving from the different PN gene expressing progenitors. The information associated to each particular subset of neuronal population will be added to the 3D-atlas (Blanc et al, eLife 2022) with the temporality and activity to generate a transcriptomic mapping over the whole hindbrain, providing the ZipSEQ for the specific neuronal circuits. We will seek whether differentiatlly expressed mRNAs display overlaping patterns in the different territories by Hybridization Chain Reaction (HCR). This will provide an incisive tool to study overlapping expression patterns, essential for unveiling regulatory interactions. We will quantify mRNA expression from the selected pools of progenitors by qHCR.
We propose complementary approaches using the zebrafish embryonic brainstem to fill the void between gene regulatory networks and circuit architecture.

The ‘Cell and Tissue Dynamics group’ headed by Dr Verena Ruprecht combines physics and biology to study the mechanisms that control cell and tissue shape, morphodynamic plasticity and multicellular self-organization in tissue development and disease

Tissues of defined shape and function are formed in the early embryo. This process requires that embryonic stem cells organize into patterns of defined architecture. At the same time cells need to acquire specific cell fates. How changes in cell shape impact on cell states and cellular signaling is still a largely open question in biology.

In this project, we will investigate how embryonic stem cells sense and respond to mechanical forces and how changes in cell shape influence cell fate specification. We have previously shown that cells use the nucleus as a mechanosensor that regulates cellular mechanics and morphodynamic plasticity (Venturini et al. Science 2020). Here we will study how nuclear mechanotransduction controls cell fate specification and pattern formation in the early embryo. We will use the Zebrafish embryo as an in vivo model system and further employ a synthetic bottom-up approach that allows to reconstitute cellular dynamics and multicellular self-organization in the early embryo. The student will apply methods from molecular biology (mRNA microinjection, cloning), embryo micromanipulation, biomimetic 3D tissue environments, advanced live cell microscopy and quantitative data analysis. The major goal of this project is to establish a quantitative description of mechanosensitive cell state dynamics in primary embryonic stem cells. This will allow to identify fundamental mechanisms that couple cell shape and cell fate specification to build the 3D body plan of the vertebrate embryo.

We are looking for a highly motivated student with an excellent academic track record who is interested to work in an interdisciplinary team and employ quantitative methods to study fundamental processes of cell dynamics in tissue development.

Alzheimer’s disease, the leading cause of dementia, affects 55 million people world-wide. Unfortunately, the search of therapies able to prevent or treat Alzheimer’s disease has faced 30 years of failed clinical trials. Familial forms of AD are caused by mutations in the amyloid-beta peptide speed up the aggregation of the peptide into amyloid fibrils. One of the challenges in developing molecules able to prevent amyloid-beta aggregation is that the process of amyloid nucleation is extremely difficult to characterise in vitro. It is even more difficult to envision methods that can do this at scale, i.e. approaches able to scan many molecules and to parallel asses their activity on all amyloid beta variants. We have developed a massively parallel reporter of amyloid nucleation which provides an excellent platform to screen for molecules and mechanisms able to prevent nucleation in vivo (Seuma et al 2021, Seuma et al 2022). This translational project will make use of this approach and combine it to an optimisation of our high-throughput in-vivo system for the uptake of small molecules

The number of female reproductive cells, called oocytes, is fixed at birth. This makes women extremely vulnerable to losing their reproductive capacity for life upon exposure to gonadotoxic (toxic to ovaries) compounds. The current gold standard to assess in vivo ovarian toxicity is ovarian histological examination of sectioned ovaries extracted from laboratory animals after repeated chemical exposure for a certain period of time (OECD protocols). Despite its widespread use, this method is labour-intensive, costly and provide heterogeneous results depending on the physiology of the animal, part of the ovary the sections came from and how they are counted.
Given these limitations of histological examination of ovaries, we have developed a semi- automated platform based on SPIM (Selective Plane Illumination Microscopy) imaging and Artificial Intelligence (AI) assisted software to image, classify and quantify oocytes in extracted whole-mount mouse ovaries (without the need for histological sections) (D’Angelo et al., in preparation). This is the first and only platform that can image and quantify oocytes in whole adult mouse ovaries without the need for intense labor and brings the much-needed efficiency, objectivity and precision to oocyte counting. This project aims to further improve our platform in order to assess the gonadotoxicity of select chemicals by treating mouse with these compounds and calculate the effect of the treatment on the number, growth and size of the oocytes in ovaries.

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 liver neutralizes endogenous and exogenous toxins and metabolites, being metabolically interconnected with many organs. Numerous clinical and experimental studies show a strong association between Non-alcoholic fatty liver disease (NAFLD) and loss of skeletal muscle mass, known as sarcopenia. Liver transplantation solves hepatic-related insufficiencies, but it is unable to revert sarcopenia. Knowing the mechanism(s) by which different organs communicate with each other is crucial to improve drug development that still relies on two-dimensional models. However, those models fail to mimic the pathological features of the disease. In this project, both tissues will be encapsulated in scaffolds in 3D using human hepatocytes and stellate cells for the liver and human myoblasts for skeletal muscle. The 3D hepatocytes will be challenged with non-esterified fatty acids (NEFAs) inducing features of Non-alcoholic fatty liver (NAFL) such as lipid accumulation, metabolic activity impairment and apoptosis. Both tissues will be integrated into a microfluidic platform, and the 3D skeletal muscle tissues will be in a metabolic cross-talk with fatty hepatocytes to induce the loss of maturation and atrophy. This study will demonstrate the connection between the liver and the skeletal muscle in NAFL, narrowing down the players for potential treatments. The tool herein presented was employed as a customizable 3D in vitro platform to assess the protective effect of albumin on both hepatocytes and myotubes.
The master’s student will be in a multidisciplinary environment and will work on tissue engineering, cell culture and characterization, microfluidics and microfabrication.

We use computational analysis of sequencing data together with population genetics predictions and statistical modeling to answer questions about mutational processes and selective pressures in cancer tumors. The ideal candidate should be highly motivated and eager to work on evolutionary and biological problems through the use and development of computational and statistical approaches.

“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. “

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 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.

Leptoquarks (LQs) are predicted by many new physics theories to describe the similarities between the lepton and quark sectors of the Standard Model and offer an attractive potential explanation for the lepton flavor anomalies observed at the LHCb experiment and the flavor factories. The discovery of LQs would represent a paradigm shift and revolutionize our understanding of how Nature operates at its most fundamental level. The ATLAS experiment at the Large Hadron Collider (LHC) has a broad program of direct searches of LQs with multiple production/decay modes in a variety of final states, with preferential couplings to tau leptons. In this project, we propose a novel and ambitious search strategy focusing on the final states including tau leptons. This project will focus on 1lepton+1tau and 2tau final states with non-resonant, singly and doubly resonant LQ production channels. Machine learning (ML) techniques will be used to define orthogonal event categories for different production modes and to discriminate the signal from background in each of these categories. The master student will perform the ML optimization studies to maximize the signal-to-background discrimination, as well as estimate the sensitivity of the search with the full Run 2 dataset. Besides gaining experience in state-of-art ML techniques and statistical methods that are of broad applicability across many research fields, the master student will be working in one of the most exciting research programs in fundamental physics at the energy frontier.

Simulations hold the key to develop new sustainable processes that can reduce climate change by reusing CO2. The project will be devoted to work in the computational study of new materials that can improve the performance converting CO2 into useful products. The project combines machine learning techniques, atomistic modeling, physics, chemistry and materials science.

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.

Ultra-cold atoms are 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 allow one to engineer a broad range of model Hamiltonians in table-top experiments. This bottom-up approach comes very close to Feynman’s idea of a “quantum simulator” – a special purpose quantum computer for solving problems out of reach for classical computers- and give access to new forms of quantum matter.

We offer Master theses in our three laboratories:

In the potassium lab, we investigate mixtures of quantum gases where the competition of interactions of different origins reveals quantum fluctuations and correlations. For instance, we exploit mixtures of Bose-Einstein condensates (BECs) to create the most dilute liquids existing in Nature [Cabrera et al., Science 359, 301 (2018)], or engineer gauge theories [Frölian et al., Nature 608, 293 (2022)] and supersolids.

In the strontium lab, we aim at synthesizing the cleanest and purest “solids”. To this end, we trap atoms in optical lattices – artificial crystals of light created by interfering laser beams – and observe how they hop from site to site by imaging them at the single-atom level. With such quantum gas microscope, we want to perform quantum simulations of the Fermi-Hubbard model [Tarruell and Sanchez-Palencia, C. R. Physique 19, 365 (2018)], which is believed to hold the key of high-temperature superconductivity.

In the Rydberg lab, we are interested in spin physics. Our goal is to develop a very flexible platform to engineer spin models, and use them to address fundamental physics problems, focusing on gauge theories for high energy physics. To this end, we constructing a new apparatus where strontium atoms will be trapped in holographically-generated optical tweezers and will interact with each other when excited to Rydberg states.

The main focus of our group is to understand how cells detect and respond to environmental changes. We have focused our studies on the characterization of the stress signal transduction pathways, especially those controlled by MAP kinases of the Hog1/p38 family, also known as the stress-activated MAP kinases (SAPK). Using S. cerevisiae budding yeast as a model organism, as well as mammalian cells, we study the molecular mechanisms required to respond to changes in the extracellular environment and which are the adaptive responses required for cell survival. Our main research lines are:

1. SAPK signaling: Using quantitative data in single cells and mathematical modelling, together with mutational analyses, we study the basic signaling properties of stress-responsive MAP pathways and how to alter them.
2. 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 characterization of the bases of adaptation in eukaryotes. We are also using genome wide CRISPR screening to identify essential genes for stress adaptation.
3. 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.
4. 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.

The recent discovery of microplastics has led to an emerging environmental concern about plastic waste accumulation in water bodies and food chain. Since these micropollutants cannot be seen by the naked eye, their detrimental effects on the environment are less obvious but still involving potential harmful risks for living organisms and human beings. This project presents an innovative concept for the removal of microplastics present in water by a sustainable photocatalytic process under visible-light irradiation over a new structural design of porous photocatalytic materials. In this approach, plastic
micropollutants will be oxidized into CO2 and water. In addition, to contribute to the development of future routes for a circular economy of plastics, their use as feedstock for the photogeneration of green fuels (hydrogen, H2) and valuable byproducts at ambient temperature and pressure will be also explored. The main goal is to use visible-light-responsive photocatalysts combined with two-dimensional (2D) nanomaterials for enhancing light harvesting and electron mobility properties, which will result in higher photocatalytic performances than those obtained with bulk semiconductors. Moreover,
a tailored intertwined and porous network of photocatalytic “inks” will be rendered by three-dimensional (3D) printing technology to retain the microplastic pieces inside the photocatalytic matrix and improve the conversion yields.

This project involves different disciplines, including materials science, chemistry, physics, engineering and technological challenges towards the development of a self-sustainable technology with a high impact on the reduction of microplastic contamination in water. Expected training outcomes: new knowledge on instrumental techniques (e.g., HPLC, Raman, mass spectrometry), forefront fabrication of structured materials (3D printing), investigation of reaction mechanisms , and fabrication of emerging 2D materials.

Accurate sequence-to-activity prediction would revolutionize protein engineering, drug development and clinical genetics. Towards the goal of accurate sequence-to-stability prediction, we are performing combinatorial mutagenesis to quantify the effects of individual mutations and their pairwise and higher order combinations on the stability of model protein domains. This allows us to both ask questions about the genetic architecture of protein stability and to test the predictive performance of various computational methods for sequence-to-activity prediction, including biophysical models incorporating pairwise and higher order energy terms inferred from the data.
To better understand and predict protein stability, we are mutagenizing the cores of small globular domains and quantifying the effects on stability of 80,000 different combinations of 5 different hydrophobic residues in 7 sites in a cell-based selection assay (Faure et al., Nature, 2022). Fitting thermodynamic models to this data allows us to infer the energetic effects of mutations and their pairwise and higher order energetic coupling terms and to evaluate different methods for predicting the effects of combinatorial sequence changes on protein stability.
While this approach is proving effective at building models with high predictive accuracy for held out data within a single dataset, an exciting question remains related to model transferability: how accurate a model trained on mutational data acquired on protein A is at predicting mutational effects on the stability of protein B? To this end, we have envisioned a dual strategy where we will assess model performance on datasets generated in isofolds (divergent protein sequences that have the same fold) as well as proteins that have increasingly divergent folds. This will contribute key information about the reach and generality of current models, thus paving the way towards the construction of a general model for protein sequence-to-stability prediction. This is a combined wet/dry lab project.

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

This MSc project will verse on understanding intracellular trafficking mechanisms, in particular that of the formation of transport carriers at the Golgi apparatus for secretion outside of the cell. The Golgi apparatus is the central organelle where secretory proteins are sorted for delivery to various parts of the cell. However, the mechanisms for such specific cargo protein (and lipid) sorting are poorly understood. The study of protein sorting at the Golgi using conventional microscopy tools has been challenging due to the highly dynamic nature and intricate morphology of this organelle. As a result, a clear understanding of the how protein sorting for secretion 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 retention using selective hooks (RUSH)-system, with state-of-the-art microscopy tools, such as stimulated emission depletion (STED) super-resolution microscopy. The data obtained will be analyzed using advanced quantitative imaging analysis to finally cast light on the mechanisms of secretory protein sorting at the Golgi.

Preventing cognitive decline and neurodegeneration is a relevant problem in biomedical research. Aging is associated to the development of neuroinflammation, which can be reduced by treatments that target the endogenous cannabinoid system. Such treatments have been found to improve synaptic plasticity and cognitive performance. We have found that synaptic transcriptional programs might be modulated by pathological and treatment conditions. In this project we will explore such transcriptional programs and validate the main observations of the transcriptomic analysis. We will use in vivo (mouse models and behavioural analysis using pharmacogenomics) and in vitro techniques (proteomics and transcriptomics of the synapse as well as immunoblot, qPCR, immunofluorescence, confocal microscopy analysis, among others) to further explore the mechanisms involved in cognitive decline and synaptic ageing, as well as the synaptic impact of treatments that improve cognition.

Proteins without stable secondary and tertiary structures, known as intrinsically disordered proteins, represent a broad part of the human proteome. In the last years, these proteins have been shown to form functional biomolecular condensates in cells via a physical process called liquid-liquid phase separation (Guillén-Boixet et al. eLife 2016, Bouchard et al. Mol. Cell 2018). This process results into the formation of a dense liquid phase where the protein is present at high concentrations. This phenomenon, however, can sometimes promote protein aggregation and a change in the physical properties of the condensates (from liquid to solid). These liquid-to-solid transitions many times result in loss of function of the protein of interest and have been related to diseases, mainly in neurodegeneration (Garcia-Cabau et al. Curr. Opin. Cell Biol. 2021). We are highly interested in understanding this process as well as finding peptides or small molecules that partition in the condensates and alter the material properties of the condensates by for example hampering liquid-to-solid transitions (Biesaga et al. Curr. Opin. Chem. Biol. 2021, Basu et al. bioRxiv 2022). Therefore, the aim of this master project is to characterise in vitro the liquid-liquid phase separation process as well as a liquid-to-solid transition of the condensates to then rationally design small molecules or peptides to target this process. For this purpose, the student will recombinantly express intrinsically disordered proteins in E. coli followed by their purification, to carry out in vitro experiments using a wide set of biophysical techniques such as light scattering, nuclear magnetic resonance, optical and fluorescence microscopy, among others.

In mammalian cells, inactivation of the Retinoblastoma protein (RB) leads to unregulated cell cycle progression promoting cell growth, genomic instability and aneuploidy, hallmarks of tumor progression. RB–mediated arrest of cell cycle progression is achieved through binding and inhibiting the E2F family of transcription factors, blocking the S phase transcriptional wave and arresting cells at the G1/S transition of the cell cycle.
Our group is ultimately interested in deciphering the mechanisms that control cell cycle progression and, more specifically, the regulatory events controlling the G1/S transition of the cell cycle in mitosis and in meiosis. We have recently determined that cells lacking CDK2 suffer a large delay in their progression through mitotic S phase and, more interestingly, are unable to complete pre-meiotic S phase. We have done a proteomic and phosphoproteomic analysis determining all the substrates of CDK2 in synchronous mitotic and meiotic cultures, isolating key targets that are phosphorylated by CDK2.
The candidate will characterize some of these substrates and the impact that their phosphorylation by CDK2 has in cell cycle progression. We plan to tackle this project from different approximations, including the generation of phospho-mutants by CRISPR and the measurement of cell cycle distribution in vivo with the use of genetically-encoded fluorescent reporters developed in our lab that allow to measure cell cycle progression.
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. Previous experience working with cell cycle will be a plus.

1) Develop a method to obtain a gold-standard of experimental amino acid profiles specific of a DNA binding from CisBP, JASPAR and HOCOMOCO.
2) Develop the construction of an amino acid profile (PWM) that specifically binds a DNA target with protein region using energies based on statitsical potentials and amino-acid preferences
3) Compare and validate the theoretical prediction with the experimental data.
4) Develop a server to obtain the theoretical amino acid profile, given a specific protein fold to bind a specific DNA sequence. A list with the best sequences preserving the fold will be downloadable.

In our research group we develop probabilistic machine learning models of biological sequences to uncover the effect of genetic variation. We are entering an era of population scale sequencing of humans, global efforts to obtain reference genomes for all life on Earth and experiments that can assay the effects of millions of genetic variants. These datasets contain the information to transform our use of genomic data in diagnosis and preventative clinical care, in protein and drug design, and much more, but we need new computational strategies to extract this information.
We are interested in how recent developments in deep learning may be adapted for modelling genetic sequence data, and how the genetic variation seen on different evolutionary timescales, from within populations to across the entire tree of life, can be used to learn about disease and molecular function.
We are looking for a researcher excited about applying statistical modelling/ deep learning to biological problems. The research project focuses on developing and applying new probabilistic machine learning models to biological sequence data to study the effect of genetic variation on all scales — from fundamental questions about gene regulation, to design of biological systems, to directly impacting the diagnostic yield of patient sequencing. To this end you will build on high-capacity methods developed by the machine learning community, together with methods from comparative genomics, population genetics and Bayesian statistics. You will work with large public datasets of human genomes, proteins across the whole tree of life and millions of experimentally assayed mutated sequences, and you will also work with data obtained by close collaborators.

We have pioneered the use of engineered tRNA chimeras (QtRNAs) to study the mechanisms of proteome quality control in human cells. We have also shown that QtRNAs can be used as tools to develop new cell-based drug-screening systems. Here, we propose to extend the use of chimeric tRNAs into the field of oncology.

Oncolytic viruses constitute a promising therapeutic strategy against pancreatic cancer. They are designed to cause cellular damage and induce a pro-inflammatory response. Here we will generate oncolytic viruses expressing QtRNAs to induce widespread proteome errors in the infected tumor cells. This will lead to cell death via apoptosis induced by the unfolded protein response, and it may also stimulate an immune response boosted by the production of neo-antigens that will increase the TMB of the tumor. Increasing the antigen load generated by tumors is a potential avenue to stimulate their elimination by the immune system. By engineering the codon content of the viral genome will ensure that the oncolytic viruses remain functional despite the generalized mutagenesis caused by the QtRNAs

Gene editing is revolutionizing bioscience and therapy. Our lab has developed a gene writing tool combining the precision of CRISPR and gene transfer capacity of a transposase (Pallarès-Masmitjà et al, Nat Com 2021) which was licensed to our lab spin off Integra Tx. We are planning to develop improved gene writers for safer and more efficient therapies with aid of the B-bio (new retrovirus-based directed evolution platform developed by our lab). A key part for the success of this massively genotype testing platform is library design and analysis using AI. Natural language processing as been very powerful to represent protein language and will be used to fuel genotypes and accelerate evolution. Coupling this biological hardware with AI will massively accelerate the evolution rate of new CRISPR based editors and writers.

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

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. We have used mouse models to demonstrate important roles for p38 MAPK signaling in tumor progression, particularly in breast, lung and colon cancer, as well as in the tumor response to chemotherapeutic drugs. Our work combines biochemical approaches and experiments in cultured cells with studies using mouse models and chemical tools. Ongoing projects in the group address the role of p38 MAPKs in two main topics: (1) Cancer cell homeostasis and chemoresistance mechanisms, and (2) Cross talk between cancer cells and stromal cells. The group has the ambition to identify new therapeutic opportunities based on the modulation of p38 MAPK signaling. We are also performing chemical and genetic screenings to find new actionable targets that can be used to boost current cancer therapies as well as to design new targeted therapies for particular cancer types.

Our lab aims to develop probes and apply chemical strategies that allow to dissect the roles of medically relevant enzymes and membrane proteins and to investigate the lipid effects on protein function. The ultimate goal of our research is to enable new therapeutic targets and biomarkers, specifically with a focus on breast cancer. To this end, we use a cross-disciplinary approach that blends molecular biology, medicinal chemistry, peptide chemistry, proteomics and cell biology. Having the use of chemical probes and tools as overarching theme, we focus on these specific projects:
1. Lipid metabolism as target for breast cancer.
2. Dissecting intramembrane proteolysis in human pathology.
3. Phage display probe development for medically relevant enzymes.

Key chemistry and technology development in this project
The driving force behind our lab’s projects is the synthesis of small molecules and the development of innovative chemistry-based technologies.
Here, you will focus on developing lipid-derived photoaffinity labels or lipid probes. These are synthetic lipid scaffolds armed with a photocrosslinker – to ensure irreversible binding to the target – and a biorthogonal handle (e.g. an alkyne) for introduction of a detection or purification tag. These probes will allow us to: 1) Map the interacting protein partners and 2) screen for inhibitors of the protein-lipid interaction which can be of therapeutic interest. More specifically, in this project you will prepare probes based on cholesterol and palmitic acid, which are two of the lipids consumed in excess in westernized diets.
What will you learn? Chemical synthesis of lipid probes, photoaffinity labeling of proteins, assay development to screen a library of small molecules and, if time, binding site mapping via proteomics.
If any of the other techniques used in the lab sparks your interest (protein expression, native nanodisc technology, phage display…) we are happy to let you explore it too.

Out of equilibrium self-assembled nanomaterials constitute a class of materials synthesized with new chemical routes. As they can reconfigure and adapt according to their environment, they constitute ideal materials for interfacing with cells for applications as drug delivery and detection systems. The characterization of their dynamic properties is challenging, due to the small size and the lack of characterization techniques with appropriate resolution and sensitivity in space and time. In this project, the scanning probe microscope (SPM) will be used to measure topographical, mechanical and dielectric properties of self-assembled nanoparticles. This project has the aim to provide functional characterization to assess how properties of these nanomaterials can affect relevant parameters in biomedicine, like the toxicity or cell entry.

The aim of this project is to obtain a multiparametric characterization of different cell properties by Scanning Probe Microscopy (SPM) and optical techniques. For this purpose, it is necessary to localize the same cell in experiments that will be performed with different equipment. The project consists in fabricating patterned and bio-compatible substrates for cell deposition, that have the characteristics of being conductive and transparent. After verification of cell deposition, SPM characterization will be performed to obtain mechanical and electrical properties on the same cell. Furthermore, confocal/optical microscopy will be added to the characterization.

The overarching aim of the project is the synthesis of molecular and supramolecular containers/receptors with polar interiors and the evaluation of their applications in molecular recognition and the development of sensors (e.g. fluorescent sensors) and sensing devices (e.g. ion-selective electrodes) for the detection of low molecular weight polar molecules related to health, metabolism and disease diagnosis.

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

Nanotechnology has had a profound impact on various fields, including materials science, electronics, medicine, and energy production. To gain a comprehensive understanding of nanomaterials and optimize their properties, it is essential to characterize their structure and composition at the atomic scale. Transmission Electron Microscopy (TEM) has emerged as a technique that allows for atomic scale imaging, coupled with spectroscopic methods such as energy dispersive X-ray spectroscopy (EDX) and electron energy loss spectroscopy (EELS), providing spatially resolved information about composition, valence state, and plasmonics and phononics. These techniques permit the correlation of physicochemical properties with atomic structure and composition, leading to a full understanding of nanoscale systems.

In this context, the student will focus on the atomic scale characterization of 1D semiconductor materials (nanowires), aiming to unravel the role of atomic arrangement in their properties, such as defect formation and elemental segregation. The project will be in collaboration with research groups from the École Polytechnique Fédérale de Lausanne or the Niels Bohr Institute of the University of Copenhagen, and experimental measurements will be conducted at the Joint Electron Microscopy Center at ALBA Synchrotron (JEMCA) using brand new TEM facilities to analyze materials at sub-nanometer scales. The student will also create 3D atomic models to simulate and interpret the acquired data.

As a summary, the student will:

1. Participate as an active member of the Group of Advanced Electron Nanoscopy of ICN2 attending to group meetings and interacting with the rest of the team
2. Adquire knowledge in aberration-corrected TEM and its associated spectroscopies
3. Adquire knowledge in data interpretation and analysis combined with the creation of 3D atomic models and simulations

Correlate the experimentally obtained atomic arrangement with the growth mechanisms and physicochemical properties of the nanostructures

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 photo and electro catalysis. The main objectives are:
– Synthesis of hybrid graphene-based lateral superlattices
– Structural and chemical characterization by scanning tunnelling microscopy (STM), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy.
-Transfer the nanomaterials and fabrication of devices for their electronic and optical characterization.
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)
– Raman spectrosocpy and luminiscence
– Electron beam lithography
– Electron transport measurements in field effect transistors.
-Ultra-high vacuum techniques (vacuum components, evaporation of precursors, single crystal preparation…)
Recent related publications of the group:
1.- M. Tenorio et al., Atomically Sharp Lateral Superlattice Heterojunctions Built‐In Nitrogen‐Doped Nanoporous Graphene. Adv. Mater. 34, 2110099 (2022).
2.- Moreno, C. et al., Bottom-up synthesis of multifunctional nanoporous graphene. Science 360, 199–203 (2018).
3.- Moreno, C. et al. On-surface synthesis of superlattice arrays of ultra-long graphene nanoribbons. Chem. Commun. 54, 9402–9405 (2018).
4.- Panighel, M. et al. Stabilizing Edge Fluorination in Graphene Nanoribbons,.ACS Nano. 14, 11120–11129 (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).

Zinc is an essential micronutrient for human health. Zinc homeostasis is tightly regulated at the systemic and cellular level. Zinc deficiency has been linked to many health disorders such as weak immunity and neurodevelopmental alterations. However, less attention has been paid to an excess in zinc supplementation and zinc toxicity. It is known that zinc as a metal, despite being considered an antioxidant agent, can lead to mitochondrial dysfunction and ROS production. In fact, there have been described processes of neurotoxicity mediated in part by zinc accumulation. In this project we aim to better understand the molecular pathways triggered by zinc excess in the context of neurodegeneration.

Ectotherms, organisms that cannot control their “body” temperature, are vulnerable to fluctuations in the ambient temperature. Eukaryotic microorganisms are especially susceptible because their survival relies on more sofisticated membrane dynamics than procaryotes. Thus, global warming is increasingly challenging the biodiversity of eukaryotic microorganisms and the continuity of the ecological functions they inherited. Unfortunately, the lack of knowledge at the molecular level about how species adapt their essential cellular processes to life-threating temperatures, hinders accurate predictions on the climate change impact and frustrates the efforts to develop remedies.

We offer a position for a master student to integrate advanced light and electron microscopy (also computational modelling if the student is interested) to investigate in situ protein networks that regulate membrane dynamics across the phylogeny of the Saccharomyces genus. The Saccharomyces genus includes S.cerevisiae, a well stablished model organism, seven additional species found in nature that have been poorly studied. Interestingly for us, the main phenotypic difference among these species is their ability to grow at different ambient temperatures. We will exploit the genus’ diversity to deliver mechanistic knowledge at the molecular scale that aids the prediction of eukaryotic microorganism biodiversity loss caused by global warming and that inspires solutions to prevent or to minimize such effects.

As a paradigm, the project will focus on the exocytic machinery, a network of 36 proteins that control exocytosis, an essential cellular process necessary for cell growth and that is conserved in all eukaryotes. Understanding how Saccharomyces species preserve exocytosis functional and which are the molecular basis that constrain such functionality to specific temperature windows will allow us to narrow the gap towards understanding the molecular bases of thermal adaptation.
With economical support, the student will learn gene editing, super resolution microscopy, particle tracking and image analysis.

Bioelectronic medicine is a research field that is experiencing a huge push in the recent years. It intends to develop devices that can communicate with cells and tissues by recording and stimulating electrical signals and promises better diagnostic and precision medicine therapies. The AEMD group at ICN2 has accumulated expertise in the development of nanomaterials and neural interfaces for advanced neural interfacing (surface and depth brain implants, peripheral nerve arrays, and optical implants among others). Key to achieve the stringent demands of such applications, is the improvement of electrode properties, particularly, achieving a high charge injection capacity.
The project will consist in exploring nanoengineering strategies to further increase microelectrode charge injection capacity and elucidating scalability rules for electrode miniaturization. Microelectrode arrays will be fabricated using nanoporous graphene thin-films and several strategies will be followed to improve stimulation performance.
The candidate will get theoretical and experimental knowledge on recording and stimulation devices for bioelectronic medicine and will gather experience on:
– Raman spectroscopy
– Atomic force microscopy (AFM)
– Scanning electrode microscopy (SEM)
– Microelectrode fabrication
– Electrochemical techniques (Impedance spectroscopy and Cyclic voltammetry)
The candidate will be carrying out his own experiments in all tasks related to the project, always with the help of experienced researchers in the Advanced Electronic Materials and Devices (AEMD) group lead by Jose Antonio Garrido at the Institute of Nanoscience and Nanotecnology (ICN2).

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.

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 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.

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.

Dried blood spot (DBS) sampling is a simple, cost-effective, and minimally invasive alternative to venipuncture for measuring exposure biomarkers in public health and epidemiological research.
The project is based on the NIH initiative ADOPT (Accumulating Data to Optimally Predict obesity Treatment Core Measures Project), that defines a set of biological parameters [i.e. adipokines, GLP-1, PYY, Insulin, Glycated hemoglobin (HbA1c), Triglycerides (TG), Tumor necrotic factor alpha (TNF-a), C-reactive protein (CRP), Interleukin 6 (IL-6), Cortisol, dehydroepiandrosterone (DHEA)] to guide the development of tailored, and potentially more effective, strategies for obesity treatment. The concept is to implement the ADOPT approach using DBS as biological matrix where to perform biomarkers analysis.
Clinical and genomic studies have shown an overlap between neuropsychiatric/ neurodegenerative disorders and insulin resistance (IR)-related somatic conditions, including obesity, type 2 diabetes, and cardiovascular diseases. Impaired cognition is often observed among neuropsychiatric disorders, where multiple cognitive domains may be affected.
The aims of the project are:
A) To develop and validate (stability and quantification) a multiple analytical approach (LC/MS/MS and multiplex IA) for the determination of biological parameters defined in the ADOPT initiative in DBS
B) To apply the DBS approach to populations of subjects with Down syndrome in the framework of the H2020 EU funded project GO-DS21 (Gene Overdosage and comorbidities during the early lifetime in Down Syndrome) interested at identifying and validate new causative mechanisms of comorbidity of obesity and intellectual disability (ID) in Down Syndrome (DS) that could be applicable beyond DS.
The familiarization with the DBS approach is very relevant in epidemiological studies and has multiple applications. The techniques used for the determination of biomarkers are state of the art and also are of general applicability in research in other contexts.

Large-scale small molecule bioactivity data are not routinely integrated in daily biological research to the extent of other ‘omics’ information. Compound data are scattered and diverse, making them inaccessible to most researchers and not suited to standard statistical analyses. We recently developed the Chemical Checker (CC), a resource that provides processed, harmonized and integrated bioactivity data on small molecules. The CC divides data into five levels of increasing complexity, ranging from the chemical properties of compounds to their clinical outcomes. In between, it considers targets, off-targets, perturbed biological networks and several cell-based assays such as gene expression, growth inhibition and morphological profiles. In the CC, bioactivity data are expressed in a vector format, which naturally extends the notion of chemical similarity between compounds to similarities between bioactivity signatures of different kinds. We showed how CC signatures can boost the performance of drug discovery tasks that typically capitalize on chemical descriptors, and we demonstrated and experimentally validated that CC signatures can be used to reverse and mimic biological signatures of disease models and genetic perturbations, options that are otherwise impossible using chemical information alone. We are now developing a generalized connectivity mapping, as a form of virtual phenotypic screening, to discover novel chemical or genetic modulators able to revert the specific signatures of disease and ‘cancel out’ the phenotypic traits of complex disorders.

The Nanostructured Materials for Photovoltaic Energy Group has more than 15-years’ experience in the synthesis of nanomaterials and their application in solar energy utilization (emerging photovoltaics, printed electronics, self-powered devices). We are working right now on Metal Halide Perovskite (MHP) solar cells and their stability, obtaining record efficiencies above 21 % and more than 10000 h stability under continuous light irradiation.
Metal halide perovskites (MHPs) represents the next big frontier in photovoltaic technologies. However, their extraordinary optoelectronic properties and the ease of band gap tunability also call for alternative utilizations. Thus, our group is also working on MHPs and MXenes for solar-driven photocatalysis to better address the big challenges ahead for eco-sustainable human activities. In this contest, MHPs structures suggest the exciting possibility for efficient solar driven H2 production and, as heterojunctions with other semiconductors (e.g., functionalized MXenes) their application in photo(electro)chemical CO2 conversion. In this project, we will synthesize novel water-stable and Pb-free MHPs and 2D MXenes to fabricate MHPs/MXene heterostructures for solar cell applications and photocatalysis.

Objective:
Synthesis of MHPs and 2D MXenes for solar energy applications.

Training outcomes:
The student will learn to synthesize and characterize nanostructured materials made of MHPs and MXenes, to process them as thin films and heterojunctions following solutions processing methods, and finally to fabricate complete photovoltaic devices and photocatalytic systems. The student will have access to diverse characterization techniques for materials and for complete device such as SEM, HRTEM, AFM, XPS/UPS, IPCE, IEC, PL, TRPL, etc. The student will have the support of a senior researcher or a Postdoc and will have to report to the group leader every week. He/She will also have to present her/his results at group meetings (English as the official language)

Our group aims at understanding how changes in light, structure and environment regulate the molecular mechanisms of photoactive (bio)molecular systems. To do so we develop and apply novel ultrafast spectroscopic tools that we combine with molecular dynamics simulations.

One goal of our group is to understand how plants thrive under natural sunlight and how we can optimise their response to sunlight changes. Indeed sunlight is a fluctuating form of energy. This means that it can suddenly spike and lead to a surplus of photoexcitations in the photosynthetic membrane, and therefore cause severe photodamage. To avoid this plants have evolved a series of ingenious mechanisms to “get rid” of the surplus of photoexcitations and, in this way, photoprotect themselves. It has been proposed that this photoprotective mechanism can be optimised to obtain more plant biomass, and therefore more food, but how can we do it?

The student will test whether it is possible to optimise photoprotection by engineering in vitro a set of photosynthetic complexes that can in principle accelerate the rate at which photoprotection is activated/deactivated, with the goal to make this rate more similar to the one of sunlight fluctuations. The student will use novel ultrafast time-resolved spectroscopy tools to determine the potential of the engineered complexes to accelerate the regulation of photoprotection.

For the student it would be beneficial to have a background in physics/chemistry/biotechnology/biology/material science or similar. The student will acquire wet lab skills, hands-on experience in protein engineering, hands-on experience on cutting-edge ultrafast spectroscopic techniques and experience in writing and presenting the research results to a multidisciplinary audience.

Molecular mechnisms underlying the phtothermal activity of an antitumoral nanomedicine.

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.

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.

Understanding Earth’s biodiversity and responsibly administrating its resources is among the top scientific and social challenges of this century. The Earth BioGenome Project (EBP) aims to sequence, catalog and characterize the genomes of all of Earth’s eukaryotic biodiversity over a period of 10 years (https://www.pnas.org/content/115/17/4325). The outcomes of the EBP will inform a broad range of major issues facing humankind, such as the impact of climate change on biodiversity, the conservation of endangered species and ecosystems, and the preservation and enhancement of ecosystem services. It will contribute to our understanding of biology, ecology and evolution, and will facilitate advances in agriculture, medicine and in the industries based on life: it will, among others, help to discover new medicinal resources for human health, enhance control of pandemics, to identify new genetic variants for improving agriculture, and to discover novel biomaterials and new energy sources, among others.
The value of the genome sequence depends largely on the precise identification 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, 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.
Within the framework of this program, there are three possible specific projects
1. Methods for genome annotation based on long read RNAseq (experimental/computational)
2. Methods for selenoprotein prediction and annotation (bioinformatics)
3. Prediction of long non coding RNAs using Machine learning approaches (ie. structured decoding from learning embedding (strongly computational)

The goal of this master thesis is to study the molecular and structural parameters governing vesicle formation for ionically-linked comb polymers (iCPs) and its exploitation to build synthetic cells capable of engulfing and killing bacteria resistant to antibiotics.
Antibiotics changed medicine and enormously positively affected the quality and extent of life. However, the current state of welfare is threatened by the emergence of bacterial strains resistant to antibiotics (AMR) that claim the lives of millions every year. Furthermore, the development of new antibiotics by pharmaceutical companies has essentially stalled due to economic and regulatory obstacles. Our group is developing a new paradigm to fight AMR using Phagocytic Synthetic Cells (PSCs). The PSCs are a new type of synthetic cells decorated with stickers and antimicrobial components. The stickers bind specifically to epitopes on the surface of a bacterium causing it to be engulfed into an endosome where the antimicrobial components tear the bacterium’s membrane, killing it. This mode of action is inspired by phagocytosis. Towards this aim, our group pioneered the development of two new classes of macromolecular amphiphiles: Janus dendrimers (JDs) and iCPs and demonstrated for the first time the engulfment of living bacteria and its killing and currently we are optimizing their use to treat and prevent infections in cystic fibrosis patients.
The specific goals of this master thesis are:
(1) Self-assembly of vesicles from iCPs, with structural variation and correlate this with the membrane thickness, bending rigidity, and overall stability
(2) Study the engulfment of 2 model bacteria
The candidate will be trained in self-assembly, confocal fluorescent microscopy and related techniques (FRAP, FRET, fluctuation analysis), AFM, DLS. Moreover, they will receive training in basic microbiology. A publication is expected at the end of the thesis.

The goal of this master thesis is to develop nanocoatings that interact with blood and modulate coagulation to improve the hemocompatibility of medical devices.
Blood clots as soon as it contacts any surface different than healthy endothelium posing serious challenges to medical devices that have to operate in continuous contact with blood such as dialysis and ECMO membranes, venous catheters, or stents, where the formation of clot can have deadly consequences. Our group has pioneered the use of antifouling polymer brushes to create stealth nanocoating to prevent the onset of coagulation and introduced the concept of adaptive hemocompatibility, where the coating use molecular switching to sense the presence of a clot and then activate blood to fight against it. In this thesis, the candidate will explore the use of polymer brushes functionalized with inhibitors of factor XIIa and tissue plasminogen activator (tPA) and their synergistic effect.
The specific goals of this master thesis are:
(1) Synthesis of antifouling polymer brushes and functionalization with coagulation inhibitors
(2) Study the ability of this nanocoatings to reduce blood activation of coagulation
(3) Study the combination of stealth properties, inhibitors of FXIIa and tPA on the self-regulated activity of the coating.
This thesis entails training in advanced polymer synthesis, characterization of nanoscale coatings (XPS, SPR, AFM) and characterization of blood-material interactions at our labs (SPR, basic hemocomp studies) as well as through our collaborators in University Clinic Aachen, Germany, ISGlobal Barcelona and Institute of Macromolecular Chemistry Prague.

Innate immune cells, such as dendritic cells, macrophages and neutrophils, control immunity and the health of organs. Therefore, they are present in virtually all tissues of the body.
We aim to understand how innate immune cells can persist in those different environments and how they can maintain and adapt their important immune functions in distinct tissues. In that regard, one of our research lines focuses on the cellular metabolism of dendritic cells, macrophages and neutrophils and its tissue-dependent adjustment. We are also interested in the cross-talk between innate immune cells and their neighbouring tissue cells, because they can affect the functionality of organs. Moreover, we are investigating how aging and chronic diseases including cancer can impact dendritic cells, macrophages as well as neutrophils and vice versa. We are examining the relevance of features of innate immune cells for pathologic progression and how those can be exploited for future therapies.
The detailed Master’s project will be designed together with the successful candidate based on her/his interests within our research lines. Our main model systems are laboratory mice and we will provide training in harvesting and processing their organs for research. Subsequent experimental techniques will include the isolation of innate immune cells for primary cell culture, flow cytometry experiments, gene expression analysis and several metabolic assays. Moreover, we offer teaching of experimental design, data analysis, visualisation and interpretation as well as help with the oral presentation of the candidate’s research results.

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

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

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

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 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.

The evolution of complex systems such as neurogenesis, carcinogenesis, and the COVID outbreak, is based on multiple interactions that are very complicated to simulate, especially if the key ingredients are hidden variables. However, they all share the fate of being subject to the principle of minimal energy, which dictates their evolution. The such principle can be linked to the symmetries of the system as a whole and can be studied using the mathematical tool of Group Theory. In this project, we will approach the evolution of such complex systems by exploring their physical properties and symmetries, and we will attempt to describe them mathematically using the elements of Group Theory. As such, a group of differential equations will be provided and related using the set of Renormalization Group Equations which will then be calibrated with related experiments during the associated Minor Project.

In the EU, fossil fuels account for the majority of energy consumption. The research into wate splitting, CO2 and nitrogen reduction, CH4 oxidation as well as electrosynthesis, has begun intensely in response to the need for the implementation of renewable energy. Our group activities are focused on developing advanced materials and novel chemistries for a variety of applications towards sustainable green energy. We are mainly working on 2D materials, conductive polymers, metal/covalent organic frameworks as scaffold and tune their photo/electroactivity using nanoparticles or molecular catalysts. These projects will undertake research into three key technical areas which are critical for the practical application of photo/electrocatalysts.
Objective 1. Exploring advanced functional materials (hybrids, composites): The main goal is to explore the potential application of emerging materials (2Ds, MOFs, COFs and conductive polymers) in the photo/electrochemical reactions. The strong dependence of the photo/electrocatalytic activity (active sites) on the size, shape, and surface structure of catalyst materials has been known for many years with elegant examples in the literature.
Objective 2. Mechanistic insights into the targeted photo/electrochemical reaction catalyzed using prepared hybrid: This objective can be achieved through the initial electrochemical tests and ex-situ characterization and the computational study. The acquired knowledge of these investigations will allow us to design a more efficient photo/electrocatalyst in terms of selectivity and stability.
Objective 3. Advanced fabrication of photo/electrodes: However, the state-of-the-art gas diffusion electrodes have been designed and optimized for high current density and low transport losses, they require further advancements and adaption to be used in different photo/electrochemical reactions due to different operating conditions and selectivity challenges. The implementation of the gas diffusion electrode (GDE) into different reaction systems can significantly improve reactant distribution.

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.

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

Congenital anomalies of the kidney and urinary tract (CAKUT) are observed in three to six per 1000 live births and account for 40-50% of the etiology of chronic kidney disease (CKD) in children world-wide. The term CAKUT includes a large variety of diverse congenital malformations (i.e., from renal agenesis and renal hypodysplasia to phenotypes primarily affecting the lower urinary tract). Importantly, in some cases CAKUT extrarenal manifestations include sensorineural hearing loss, retinal and brain malformations. Interestingly, many of the 40 established monogenic causes of human CAKUT were initially derived as candidate genes from observations in mouse models of CAKUT and subsequently screened for their prevalence in human disease cohorts. However, the insights from mouse models, do not always directly translate to human genetics. Explanations for this discrepancy include potential species-specific differences kidney and urinary tract development, alterations in the required gene dosage, functional compensation by redundant genes, among others.

Interestingly, and with regards to the diverse manifestations of CAKUT, these are thought to result from disturbances at any point in renal morphogenesis. The possibility  to generate human pluripotent stem cells (hPSCs) derived organoids has opened new venues for the study of human development and disease. In this regard, we have developed a robust protocol for the generation of three dimensional kidney derived organoids from hPSCs containing different cell subtypes from the functional nephron (i.e., tubular epithelial cells, glomerular cells, interstitial fibroblasts, among others). Moreover, we have shown on the application of emerging technologies from tissue engineering field to construct heart, retinal and renal analogues suitable for kidney disease modeling. More recently we have proved, for the first time, on the utility of kidney organoids to model human disease (including SARS-CoV-2 infection and diabetic-like responses in these models).

Building upon these findings here we aim to interrogate how experimentally induced CAKUT conditions result in alterations in kidney, heart and retinal development. We will first generate unique hPSCs lines capturing CAKUT genetics taking advantage of our recently developed CRISPR/Cas9 platform in hPSCs. These unique cell lines will be used to generate hPSCs-kidney organoids based in the host laboratory expertise. Profiting this unprecedented experimental setting we will explore on the interplay of environmental factors at different stages of nephron, cardiac and retinal development in wild type and CAKUT-genetic backgrounds. Using single cell profiling (including scRNAseq and scATACseq) we will be able to identify putative markers of CAKUT initiation. Top candidates will be validated in CAKUT biopsies from patients. Top hits will be assayed for compound screening in wild type and CAKUT-kidney and retinal organoids aiming to identify common and unique alterations in these tissues during CAKUT initiation.

Worldwide energy consumption requires energy vectors capable to store and distribute energy for many applications for which direct electrification or battery storage is not suitable. Solar synthetic fuels, based on the photoelectrochemical (PEC) conversion and storage of solar light in the chemical bond of molecules such as H₂ or other carbon-based fuels allows for long term storage and distribution, identified as a key scientific and technological field by the EU. Tandem PV-PEC structures have been largely researched using metal oxide photoelectrodes, but large bandgaps and recombination rates limit their performance to few milliamperes. Taking advantages of the advancements of organic photovoltaics (OPVs), tuneable band gap photoelectrodes and photovoltaic cells can be fabricated with competitive photocurrents if adequate polymers and blends can be selected.

We propose the fabrication of organic solar cells based on water-stable polymers and blends, to be studied in photoelectrochemical environments (OPECs), in tandem with other organic PVs, where the light has been computationally simulated to be optimally balanced with 1D multilayer Bragg reflectors. Hole and electron-selective (HTL and ETL metal oxides) thin-film filter contacts will be used to increase the charge separation and extraction. If the project moves fast, corrosion-protective strategies will be implemented and oxygen mediators studied.

The candidate will join the state-of-the-art laboratory of a multidisciplinary group at ICFO which will provide with expertise on light management nanostructures (computationally simulated and fabricated) for organic solar cells and photoelectrochemical applications in H₂ or CO₂RR. Fabrication hands-on experience (Sputtering, evaporation, spin-coating, etc), clean-room fabrication facilities and glove-box, nanoscale characterization techniques (SEM, XRD, ellipsometry, profilometry, etc) and testing stations (Solar simulators, spectrometers, irradiometers, etc) will also be provided.

* Required skills: basic knowledge of optics, thin film fabrication, semiconductors absorbers and (organic) photovoltaic solar cells is valuable. Although, the group searches for highly motivated candidates and will provide all necessary training for the highly multidisciplinary field of photoconversion of solar light into highly valuable solar fuels.

Lipid peroxidation is a process in which oxidants attack lipids containing carbon-carbon double bounds, creating hydrophilic moieties that dramatically alter the properties and mechanical behaviour of lipid membranes. Several studies have shown that the effect of oxidized lipids on membrane organization is key in controlling signalling pathways, homeostasis and in the onset of several diseases. However, the relationship between the effects of lipid peroxidation on the mechanical properties of the membrane and the reorganization and dynamics of mechanosensitive proteins is poorly explored.

This project aims to study the effects of controlled photo-oxidation processes on the mechanical properties of lipid membranes and understand how they translate into the interactions and organization of force-sensitive proteins. In the first stage, the project will focus on the induction and characterization of lipid peroxidation using model lipid vesicles. For this, the candidate will explore different fluorescent sensors and photosensitizing compounds, combining photophysical methods and fluorescence microscopy techniques, with particular emphasis on fluorescence lifetime imaging (FLIM). In the second stage, the knowledge acquired will be applied to study the effects of lipid peroxidation in living mammalian cells. The candidate will explore how oxidative damage alters the properties of the membrane and the concomitant cellular responses. Specifically, we are interested in characterizing the organization and dynamics of mechanosensitive proteins located at the plasma membrane induced by controlled and localized photo-oxidation processes.

Candidates should have a degree in Chemistry, Biochemistry, Biophysics, Bioengineering or a related field. Experience in at least one of these areas is highly desirable: fluorescence microscopy, lipid membranes, cell culture and membrane biophysics. Fluency in English is required.