Master of Multidisciplinary Research in Experimental Sciences - Major Project List 2020/2021
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Master of Multidisciplinary Research in Experimental Sciences Major Project List 2020/2021 bist.eu/master
Major Research Projects A key feature of the program is in-depth Major Research Project: 6-month long hands-on research training in multiple project carried out under the supervision. fields. Students undertake a 6-month long Upon completion of the project, the major project (Major Research Project) student will write a research paper and and a 10-week minor project, in two publicly defend the work he or she has different research disciplines in leading done. research institutions. Students are Minor Research Project: 10-week long provided with extensive training in research project, complementary to the professional research skill, and engage student’s major research project, carried directly with and learn from outstanding out in a different research laboratory. local and international researchers of a PI Upon completion of the project, the from one of the participating institutions. student will prepare a poster and publicly defend the work he or she has done. Information for Applicants *Applicants are requested to list 5 major **Second Call applicants who state projects in order of preference. The preference for a project assigned in the Selection Committee will assign major previous round will be informed and projects based on said list as well as the requested to submit new projects before Committee’s evaluation of the student’s the closing of the call. candidature, the supervisors’ assessments and the adequacy of the project to the candidate’s profile.
Master of Multidisciplinary Research in Experimental Sciences Major Research Projects BIST-UPF 2020/2021 LIST OF PROJECTS THE DEPARTMENT OF EXPERIMENTAL AND HEALTH SCIENCES (DCEXS-UPF) ......................7 DCEXS-2001. Translational Synthetic Biology .................................................................................7 DCEXS-2002. Dynamical Systems Biology .......................................................................................7 DCEXS-2003. Uncovering the clonal dynamics of the hindbrain: balancing proliferation 3 and differentiation ...............................................................................................................................8 DCEXS-2004. Molecular Physiology Laboratory .............................................................................9 DCEXS-2005. Zinc imbalance and cancer progression ............................................................. 10 DCEXS-2006. Integrative Biomedical Materials and Nanomedicine Lab ............................. 10 DCEXS-2007. Hypoglycosylation Of Voltage-Gated And Mechanosensitive Ion Channels: New Pathological Mechanisms And Therapeutic Targets For Neurological Disorders In Phosphomannomutase 2 Deficiency (PMM2-CDG) .................................................................... 11 DCEXS-2008. In vivo mapping of the neuronal circuity related to vestibular and auditory sensory function ................................................................................................................................. 12 DCEXS-2009. Monitoring oxidative stress in living cells – use of genetically encoded reporters to determine H2O2 levels linked to signalling and disease ................................. 12 DCEXS-2010. Engineering Intracellular Nanotools To Image Protein Structures In Vivo: Resolving The Mechanism Of Exocytosis ..................................................................................... 13 DCEXS-2011. Cancer Biology .......................................................................................................... 13 CENTER FOR GENOMIC REGULATION (CRG) ...................................................................... 15 CRG-2001. Reconstituting tissue self-organization and collective cell dynamics in early embryonic development via 3D synthetic culture methods ..................................................... 15 CRG-2002. Trans-generational epigenetic influences on mutation outcome ....................... 15 CRG-2003. Understanding the molecular basis of neuronal 3’UTR length-dependent mRNA sorting ..................................................................................................................................... 16 CRG-2004. Understanding the molecular basis for bidirectional neuronal mRNA transport .............................................................................................................................................................. 17 CRG-2005. X-chromosome reactivation in iPSCs and mouse embryos ................................. 18 CRG-2006. Epigenetic reprogramming in mammalian germ cells ......................................... 18 CRG-2007. Dynamics of Living Systems ........................................................................................ 19
INSTITUTE FOR BIOENGINEERING OF CATALONIA (IBEC) .................................................. 20 IBEC-2001.Nanoprobes & Nanoswitches I ................................................................................... 20 IBEC-2002. Nanoprobes & Nanoswitches II ................................................................................. 21 IBEC-2003. Nanoprobes & Nanoswitches III ................................................................................ 22 IBEC-2004. Improving site-specific targeting of nanomedicines for treatment of lung or brain diseases ................................................................................................................................... 22 IBEC-2005. Development of computational Solutions for Ion Mobility Spectrometry Data Analysis ............................................................................................................................................... 23 IBEC-2006. Equivalence of chemical measurement methods .................................................. 24 IBEC-2007. Integrative Cell and Tissue Dynamics ...................................................................... 24 IBEC-2008. Smart Nano-Bio-Devices I ............................................................................................ 25 IBEC-2009. Smart Nano-Bio-Devices II ........................................................................................... 25 IBEC-2010. Selection of DNA aptamers against Plasmodium falciparum early blood stages .................................................................................................................................................. 26 IBEC-2011. Bacterial infections: antimicrobial therapies I ........................................................ 27 IBEC-2012. Bacterial infections: antimicrobial therapies II ....................................................... 27 IBEC-2013. Deep Mutagenesis of Prion-Like Domains............................................................... 28 IBEC-2014. Nanoscopy for Nanomedicine.................................................................................. 28 IBEC-2015. Developing organ-on-a-chips for the study of diabetes type II .......................... 29 THE INSTITUTE OF PHOTONIC SCIENCES (ICFO) ................................................................. 31 ICFO-2001. Live Cell Superresolution Microscopy & Embryonic Stem Cells ......................... 31 ICFO-2002. Medical Optics I ........................................................................................................... 32 ICFO-2003. Medical Optics II .......................................................................................................... 32 ICFO-2004. Medical Optics III ......................................................................................................... 32 ICFO-2005. Medical optics group IV ............................................................................................. 33 ICFO-2006. All-optical interrogation of synaptic transmission in C elegans......................... 33 ICFO-2007. Engineering superconductivity in twisted bilayer graphene. .............................. 34 ICFO-2008. Hot Atoms 1 ................................................................................................................... 34 ICFO-2009. Quantum simulation with ultracold atoms .............................................................. 35 ICFO-2010 Single-molecule microscopy tools to study intra-Golgi membrane traffic ........ 36 ICFO-2011. Attosecond Molecular-movies with Inner-Shell Electrons ..................................... 37
Master of Multidisciplinary Research in Experimental Sciences Major Research Projects BIST-UPF 2020/2021 ICFO-2012. Real time 3D video tracking of nanoparticle motion confined in an optical trap ....................................................................................................................................................... 37 ICFO-2013. Frontiers of Quantum Information Science, Quantum Simulations and Many Body Physics ....................................................................................................................................... 38 ICFO-2014. Cavity quantum electrodynamics.............................................................................. 38 ICFO-2015. Hyperfocusing infrared light for sensitive photodetection .................................. 39 ICFO-2016. Single photons from two-dimensional materials ................................................... 39 5 INSTITUTE OF CHEMICAL RESEARCH OF CATALONIA (ICIQ) .............................................. 41 ICIQ-2001. Machine Learning Techniques in Electro-Catalysis................................................ 41 ICIQ-2002. Nanomaterials for energy applications ................................................................... 41 CATALAN INSTITUTE OF NANOSCIENCE AND NANOTECHNOLOGY (ICN2) ...................... 42 ICN2-2001. Advanced Electron Nanoscopy ................................................................................. 42 ICN2-2002. Atomically precise graphene nanostructures for optoelectronics ..................... 43 ICN2-2003. Complex Inorganic Nanocrystals For Artificial Photosynthesis, Biogas Production And Fuel Cells ............................................................................................................... 44 ICN2-2004. Nanoremediation: Emerging-Micropollutants And Nanopharmaceuticals ...... 45 ICN2-2005. New Transfection Agents And Nanoparticle-Antioxidant Adjuvants For Inflammatory Related Diseases ..................................................................................................... 46 INSTITUTE FOR HIGH ENERGY PHYSICS (IFAE) .................................................................... 47 IFAE-2001. Enhanced ATLAS Level-1 trigger capabilities with Artificial-Intelligence regression on Field-Programmable Gate Array architecture. ................................................. 47 IFAE-2002. Impact of high-granularity timing detectors in the search for the Standard Model Higgs boson produced in the vector boson fusion process and decaying into a pair of tau leptons ............................................................................................................................ 47 IFAE-2003. Commissioning of the first Large-Size Telescope of the Cherenkov Telescope Array..................................................................................................................................................... 48 IFAE-2004. Quantum annealing with coherent superconducting qubits ................................ 48 IFAE-2005 Large-scale correlations and cancer cell metastasis ............................................. 49 IFAE-2006 Fractal dynamics and cancer growth ........................................................................ 50 IFAE-2007 Avalanche Photodiodes for Medical Diffuse Optics ............................................... 50 IFAE-2008 The PAU Survey: the potential of narrow-band observations for revealing the true panoply of different galaxy types ......................................................................................... 51
IFAE-2009 Gravitational Waves detection using Deep Learning with LIGO/Virgo data ... 51 IFAE-2010 The ESA Euclid Dark Energy Survey ............................................................................ 52 INSTITUTE FOR RESEARCH IN BIOMEDICINE (IRB BARCELONA)......................................... 53 IRBB-2001. Development and Growth Control Laboratory ....................................................... 53 IRBB-2002. MMB ............................................................................................................................... 54 IRBB-2003. Understanding stress adaptation from yeast to mammalian cells.................... 54 IRBB-2004. Cell Division Laboratory .............................................................................................. 55 IRBB-2005. Complex metabolic diseases and mitochondria ................................................... 55 IRBB-2006. Signalling and Cell Cycle ............................................................................................ 56 IRBB-2007. Biomedical Genomics .................................................................................................. 57
Master of Multidisciplinary Research in Experimental Sciences Major Research Projects BIST-UPF 2020/2021 THE DEPARTMENT OF EXPERIMENTAL AND HEALTH SCIENCES (DCEXS-UPF) develop precise genetic methodologies to modulate skin microbiome population to DCEXS-2001. Translational Synthetic enable novel therapeutic strategies for Biology skin disease and wellbeing. Keywords. CRISPR, synthetic biology, 7 Supervisor. Marc Güell genetic engineering, gene therapy, Research group. Translational Synthetic microbiome Biology Project Description. Our group aims to DCEXS-2002. Dynamical Systems Biology leverage synthetic biology and gene editing to generate technologies with Supervisor. Jordi Garcia-Ojalvo therapeutic potential. Our ability to modify genomes has profoundly affected how we Research group. Dynamical Systems perform scientific research, and future Biology therapies. Emergent consequences of Project Description. The Dynamical reinventing biology have already started Systems Biology laboratory of the to reach society. For example, engineered Universitat Pompeu Fabra studies the human immune T cells (CAR-T) cure dynamics of living systems, from cancers with outstanding performance, or unicellular organisms to human beings. ‘ex vivo’ applied gene editing The lab uses dynamical phenomena to technologies have successfully cured identify the molecular mechanisms of a severe genetic diseases such as ‘bubble large variety of biological processes boys’ or sickle cell disease. Biological including cellular decision-making, spatial technology will have a growing influence self-organization and tissue homeostasis. in our lives. We have lines of research in We use experimental biochemical and developing precise tools for applied gene electrophysiological data to constrain editing technologies and in skin computational models of living systems, microbiome based therapeutics. and thereby unravel the underlying -Precise editing of mammalian genomes: molecular circuitry of physiological Despite enormous progress, precise processes. Using a combination of introduction of new alleles in mammalian theoretical modelling and experimental genomes still results difficult. Our goal is to tools including time-lapse fluorescence explore novel alternatives to precisely re- microscopy and microfluidics, we write genomes safely and efficiently. investigate dynamical phenomena such -Microbiome engineering: The skin is as pulses and oscillations, and study how populated by numerous microorganisms multiple instances of these processes which affect host health. We aim to coexist inside cells and tissues in a coordinated way. At a larger level of
organization, we use conductance-based The specific objective of the project is to neural models to explain the emergence uncover the clonal growth dynamics of the of collective rhythms in cortical networks, hindbrain in order to understand how cell and mesoscopic neural-mass models to proliferation and cell differentiation are link the structural properties of brain balanced. For this we will life-monitor the networks with their function. whole embryonic hindbrain upon time and compare the growth of specific progenitor Keywords. Quantitative biology, cell populations with the overall growth, biophysics, statistical physics, nonlinear using genetic clonal experiments dynamics, complexity combined with a Machine Learning platform for their analysis. These results will provide us insights into the DCEXS-2003. Uncovering the clonal mechanisms of segregation of progenitors dynamics of the hindbrain: balancing within the hindbrain and how brain proliferation and differentiation morphogenesis and growth are coordinated. Supervisor. Cristina Pujades To explore how different groups of Research group. Development of the progenitors contribute to the growth of the Central Nervous System hindbrain, zebrafish transgenic embryos Project Description. Our main goal is to will be used allowing for fluorescent life- understand how spatiotemporally monitoring clonal growth. To get insight coordinated cell progenitor specification into the growth of the tissue and the and differentiation occurs alongside specific progenitor cell populations we will morphogenesis to construct the functional assess: i) clonal growth, and ii) brain. Thus, we need to blend the morphological spatial variability of the information provided by morphogenesis clones. Clone tracking will allow and tissue growth studies -balancing deciphering modes of clonal behaviour progenitors vs. differentiated cells-, with (symmetric vs. asymmetric divisions). We the reconstruction of cell lineages, with the will develop a Machine Learning demand to incorporate the time as a approach for cell motion pattern crucial factor. We make use of the recognition and allocation, since an zebrafish embryo because it allows to automatised, accurate segmentation and combine high-resolution in vivo imaging tracking framework will represent an with the genome-editing technology. We improvement to identify distinct modes of take advantage of complementary growth and movement patterns. approaches such as 4D-imaging, The student will learn the experimental functional perturbations, clonal growth skills for 4D-imaging and cell-tracking, and studies and transcriptomics in order to fill the computational tools to extract the void between gene regulatory biological insights from big-data analyses. networks and tissue architecture. Keywords. brain morphogenesis, 4D- imaging, zebrafish, clonal growth
Master of Multidisciplinary Research in Experimental Sciences Major Research Projects BIST-UPF 2020/2021 Peroxynitrite stabilizes Aß oligomers, the most toxic forms of Aß aggregates, DCEXS-2004. Molecular Physiology impairing NMDA Rc function. Laboratory - We have designed synthetic peptides Supervisor. Francisco José Muñoz with a sequence similar to that of albumin that impairs amyloid aggregation in brain. Research group. Molecular Physiology C-term from albumin impairs Aß Laboratory aggregation and protects neurons. 9 Project Description. 4. Expected training outcomes: 1. Group: Dr. Francisco J. Muñoz - To acquire the necessary skills to become (University lecturer; Pubs: 64; Total an independent researcher in the field of Citations: 2244; h-index: 25) is focused on neurodegeneration. the study of the production, aggregation and cytotoxicity of amyloid ß-peptide (Aß) - To reach scientific goals in a high quality in Alzheimer’s disease (AD) and its environment through a laboratory regulation by oxidative stress and nitric equipped with state-of-the-art equipment oxide. for the biochemical, neurobiology 2. Proposed Project: AD is due to the Aß (imaging, tissue culture) and aggregation inside the brain. Aß is electrophysiology studies. produced by the enzyme BACE1 that - To expand considerably his/her scientific cleavages the amyloid precursor protein and technological base. (APP). Both APP and BACE1 are localized in the lipid rafts enriched with GM1 - To achieve not only an assortment of both ganglioside. GM1 has been suggested to theoretical and practical aspects of favour Aß aggregation therefore research but also the critical thinking and contributing to synaptic impairment. We managing skills necessary to move his/her propose that during aging there is a GM1 scientific career forward and become an increases. Thus GM1 clusters could be international scientific researcher. promoting BACE1 amiloydogenic activity. Keywords. Alzheimer's Disease; Amyloid; An increase of the concentration of Aß in GM1; hippocampal neurons; aging neuron extracellular matrix will favour Aß oligomerization by binding GM1. 3. Preliminary results: - Aged primary cultured of hippocampal neurons have high levels of GM1. - The binding of Aß to GM1 is increased when asialyzated. - Aggregated Aß in synapses favours the production of nitro-oxidative stress.
DCEXS-2005. Zinc imbalance and cancer DCEXS-2006. Integrative Biomedical progression Materials and Nanomedicine Lab Supervisor. Rubén Vicente García Supervisor. Pilar Rivera Gil Research group. Laboratory of Molecular Physiology-Biophysics of the immune Research group. Integrative Biomedical system Materials and Nanomedicine Lab Project Description. The human body Project Description. Our research lies at contains 2–3 g of zinc. In the cell, aside the crossroads between nanoscience and from being a structural component of biomedicine, the field of nanobiomecine. many proteins, zinc plays a role as a We convert basic research findings on second messenger regulating different nanobiotechnology into new approaches signalling cascades involved in addressing biomedical challenges. We proliferation, migration and fabricate multifunctional biomaterials by differentiation. Several transporters (Zip integrating selected building-blocks into and ZnT family) and zinc binding proteins one single system depending on the work in a coordinated way to tightly application's requirements and regulate cytosolic zinc concentrations. Zinc considering the biophysicochemical dysregulation has been described in properties of the nanomaterial. We target several kinds of cancers affecting both, independently two areas: diagnostics and the patient zinc serum levels and tumour therapeutics of diseases but also zinc content. The expression of certain zinc simultaneously by creating a theranostic transporters has been correlated with the tool towards a more personalized stage, progression of tumours and medicinal approach of diseases. We focus acquisition of pro-metastatic features. on understanding and engineering the However, the underlying mechanisms nanomaterial-biological system interface. behind zinc imbalance and cancer We use state of the art material and progression are not fully understood. The biological/molecular characterization project is based on a multidisciplinary methods to find predictive patterns of approach combining molecular biology, cellular outcomes after exposure to biophysics and nanotechnology. The nanomaterials for translational medicine. students will acquire skills in different The main research lines are: techniques of all these different disciplines. Engineering nanomaterials for diagnosis/sensing Keywords. zinc, cancer, transporter, Engineering nanomaterials for controlled metastasis release . Exploring the therapeutic value of novel nanomaterials Engineering the nanomaterial-biological interface
Master of Multidisciplinary Research in Experimental Sciences Major Research Projects BIST-UPF 2020/2021 Keywords. Nanomedicine; Optical CDG patients. In this respect, biosensing; Nanomaterials; Controlled mechanosensitive Piezo channels have release; Theranostics been suggested to underlie the transduction of different mechanical forces into a variety of neurological responses in DCEXS-2007. Hypoglycosylation Of the brain. Voltage-Gated And Mechanosensitive Our overall objective is to study how Ion Channels: New Pathological hypoglycosylation affect the function of 11 Mechanisms And Therapeutic Targets neuronal CaV2.1 and Piezo channels, and For Neurological Disorders In its relevance in neurological alterations Phosphomannomutase 2 Deficiency linked to PMM2-CDG by using (PMM2-CDG) heterologous expression systems and Supervisor. José Manuel Fernández neurons from wild-type and PMM2-CDG Fernández knock-in mice. Similar analysis will be Research group. Laboratory of Molecular performed in fibroblasts of patients with Physiology PMM2-CDG and healthy volunteers, and iPSC-derived neurons from those Project Description. fibroblasts, to directly assess the degree "Phosphomannomutase Deficiency of hypoglycosylation and dysfunction of (PMM2-CDG) is the most frequent CaV2.1 and Piezos in patients with distinct congenital disorder of N-linked neurological phenotypes (moderate glycosylation (CDG). PMM2-CDG versus severe), and initiate a study of symptoms include severe neurological correlation with their clinical and genetic alterations. Progressive atrophy of the report. Finally, we will test the capability of cerebellum is usually found in all PMM2- novel CaV2.1 modulators to revert CDG patients, leading to the ataxia hypoglycosylation effects, thus cerebellar syndrome. Also, the stroke-like establishing a proof of concept to develop episode (SLE) is one of the unpredictable in the future a specific treatment for and serious neurological complications neurological events in PMM2-CDG." occurring in PMM2-CDG. Mechanisms Keywords. Hypoglycosylation; neuronal underlying both SLE and cerebellar voltage-gated calcium channels; syndrome in PMM2-CDG are unknown and mechanosensitive Piezo channels; there are no guidelines for their Phosphomannomutase Deficiency (PMM2- prevention, detection and treatment. We CDG); electrophysiology have recently identified the neuronal voltage-gated Ca2+ channel CaV2.1 as a potential target of glycosylation defect in the Central Nervous System of PMM2-CDG patients, and an important contributor to SLEs and cerebellar syndrome in PMM2- CDG. Besides, we found that mild cranial trauma is a potential SLE trigger in PMM2-
DCEXS-2008. In vivo mapping of the activated in order to integrate neuronal neuronal circuity related to vestibular circuit maps with behaviour output. We and auditory sensory function aim for a student highly motivated in neurobiology, imaging and circuitry to undertake this challenging project. Supervisor. Berta Alsina Keywords. optogenetics, in vivo imaging, Research group. Morphogenesis and Cell neural activity, zebrafish Signaling Sensory Systems Project Description. The inner ear capturing auditory and balance DCEXS-2009. Monitoring oxidative stress information though specialized hair cells in living cells – use of genetically transmits the sensory information to the encoded reporters to determine H2O2 brain through bipolar neurons. We have levels linked to signalling and disease investigated though high-resolution imaging and genetic perturbations the Supervisor. Elena Hidalgo development of the sensory neurons of the inner ear in zebrafish (Hoijman et al. 2017 Research group. Oxidative Stress and eLife, Taberner et al. biorxiv). This Cell Cycle Group information is currently also being Project Description. General objectives: mapped with spatial transcriptomic data Intracellular peroxides are important to discriminate between different neuronal drivers of both toxicity and signalling subtypes. However, it remains unexplored events. Several genetically encoded how different stimuli activate specific fluorescent probes have been developed neurons of the ganglion and how neuronal to monitor H2O2 fluctuations in response activity is mapped into the brain. Neuronal to endogenous and exogenous oxidant activity can be monitored in vivo by the sources. We have recently developed a use of GCAMP, a genetically encoded new reporter, based on the fission yeast calcium sensor. The project aims at H2O2 sensor Tpx1 fused to a redox imaging at high spatial and temporal sensitive GFP, which is more sensitive to resolution the patterns of neuronal activity peroxide fluctuations that any other in the statoacoustic ganglion and the reporter characterized so far. We aim at hindbrain when specific neurons are comparing its behaviour in response to activated or specific stimuli are presented genetic and environmental interventions. to the zebrafish. For this aim, the student The candidate will characterize the will use a transgenic line expressing regulation of our H2O2 reporter in GCAMP5G in neurons, will learn how to different S. pombe backgrounds and in image neuronal activity in vivo and will different biological situations, such as collaborate with a laboratory with during chronological aging or cell cycle expertise in photochemically activation of progression, to assess the role of neuronal receptors. Moreover, analysis of moderate intracellular H2O2 fluctuations behaviour will also be assessed when as drivers of these processes. specific populations of neurons are
Master of Multidisciplinary Research in Experimental Sciences Major Research Projects BIST-UPF 2020/2021 Furthermore, an unprecedented Therefore, to undertake future experiment in the redox field will be to use investigations relevant for biomedicine it our fluorescent reporter in different will be necessary to perform structural biological models (ranging from bacteria biology experiments in living cells. to human cells), to compare intracellular The aim of the project is to develop new H2O2 levels using the same protein genetically-encoded nanotools to boost sensor. the power of quantitative fluorescence Expected training outcomes: training on microscopy. In collaboration with the 13 cellular biology, molecular biology and group of Alex De Marco, at the Monash fluorescence microscopy will be acquired University (Australia), we will also asses during project execution. the implementation of these new nanotools in cryo-electron tomography. Keywords. Redox biology, aging, H2O2, During the progression of the project the yeast student will acquire a strong expertise in DCEXS-2010. Engineering Intracellular gene editing tools, advanced light Nanotools To Image Protein Structures microscopy and image analysis. In Vivo: Resolving The Mechanism Of Depending on the student’s skills and Exocytosis interest, the project could also involve in silico integration of acquired data to model 3D structures of large protein Supervisor. Oriol Gallego complexes controlling cell growth. Research group. Live-cell Structural Keywords. Genetic engineering, light Biology microscopy, molecular mechanisms, cell Project Description. Our group develops growth new methods of fluorescence microscopy that allow the study of macromolecular complexes directly in living cells beyond DCEXS-2011. Cancer Biology the limits of current approaches. Understanding the molecular mechanisms Supervisor. Ana Janic that drive life (and those that lead to Research group. Cancer Biology death) requires structural characterisation of the protein machinery sustaining the Project Description. The tumour biology of the cell, both in a healthy and suppressor gene p53 is mutated in half of in a pathological situation. Historically, the human cancers. Given the difficulties in structural biology has been largely developing strategies for targeting wild- centred around in vitro approaches. type or mutant p53, further understanding However, the degree of knowledge of its basic biology is required for acquired to improve human health will be successful clinical translation. The present determined not only by the precision of the project focuses on understanding the experimental measurements but also by complexity of the p53 network in tumour their proximity to a physiological context. 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. The successful candidate will be involved in the use of a wide variety of experimental techniques, including mouse models of cancer, tissue/tumour pathology, CRISPR-Cas9 gene-editing technology, next-generation sequencing, molecular biology, cell culture and flow cytometry. Keywords. Cancer, tumour suppression, p53, DNA damage
Master of Multidisciplinary Research in Experimental Sciences Major Research Projects BIST-UPF 2020/2021 CENTER FOR GENOMIC REGULATION (CRG) CRG-2001. Reconstituting tissue self- signals to instruct cell fates and dynamic organization and collective cell cell behaviour. Recent work from our lab dynamics in early embryonic has identified that mechanical tissue development via 3D synthetic culture crowding and geometrical boundary methods constraints from the 3D tissue environment Supervisor. Verena Ruprecht critically influence dynamic cell migration 15 behaviour (Ruprecht et al., Cell 2015). Research group. Cell and Tissue These results highlight the relevance of Dynamics mechanosensitive signalling pathways Project Description. The Ruprecht lab and cellular adaption to physical tissue studies multi-scale dynamics of cell and parameters in early embryogenesis. In this tissue organization in early research project, we will address how embryogenesis. We have a key focus on multicellular tissue dynamics and self- understanding biological self- organization is controlled by mechanical organization, cell and tissue shape and physical processes in early formation and dynamic cell behaviour in embryogenesis. We aim at identifying key 3D tissues. Our lab follows a highly molecular and cellular modules that interdisciplinary approach combining enable cellular information processing of molecular and cell biological tools with physical tissue parameters and how they advanced biophysical methods and regulate single and collective cell quantitative live cell imaging approaches. dynamics to build the shape of an embryo. In this research project, we will establish Keywords. Biological Self-organization, synthetic 3D culture methods that enable Multicellular dynamics, Cytoskeleton, to mimic tissue self-organization of early Mechanobiology, Biophysics embryonic development in synthetic culture environments. During gastrulation, an unstructured mass of pluripotent CRG-2002. Trans-generational embryonic stem cells undergoes cell fate epigenetic influences on mutation specification and acquires a defined outcome shape, laying the foundation for the future body plan. Morphodynamic shape Supervisor. Ben Lehner formation depends on precise spatio- temporal positioning of three distinct germ Research group. Genetic Systems layers (mesoderm, ectoderm and Project Description. "Many detrimental endoderm) that give rise to different mutations only cause disease in a subset organs of the organism. Both chemical of their carriers, a phenomenon known as signals (morphogens) and physical stimuli incomplete penetrance. Further, (as geometry, cell density, adhesion and individuals often display variable cell deformation) serve as information expressivity of a disease, ranging from
mild to severe health impairments. Animal CRG-2003. Understanding the molecular studies show that incomplete penetrance basis of neuronal 3’UTR length- and variable expressivity are still present dependent mRNA sorting in the absence of environmental or genetic variation, with inter-individual Supervisor. Sebastian Maurer variation in gene expression during development able to predict to some Research group. Cytoskeleton dependent extent whether an individual is affected or RNA localisation mechanisms not by an inherited mutation [1, 2]. We Project Description. The Maurer Lab hypothesized that an additional influence wants to understand the biochemical on mutation penetrance and expressivity processes that drive the generation of might be the environment or physiological neuronal mRNA distributions. Thousands state of an individual’s parents or even of mRNAs are transported into axons and previous generations. To test this dendrites and their local translation at the hypothesis, we have established an right location is important for neuron automated screening platform to quantify development, polarization and synaptic how environmental perturbations in plasticity which underlies long-term previous generations influence the memory formation. How motor proteins outcome of inherited mutations in C. such as kinesins and dynein recognise elegans. We identified several their mRNA cargo and transport them to environmental factors that altered their destination is not understood. The mutation outcome in subsequent Maurer lab develops new single-molecule generations that were never directly assays in microfluidic chambers to exposed to the environmental challenge. assemble neuronal mRNA transport Your master thesis project will investigate complexes from purified components. possible molecular mechanisms Through this approach, the Maurer Lab underlying the multi-generation memory of recently revealed the essential building environmental perturbations. To this end, blocks of a minimal mammalian mRNA you will use transgenic C. elegans lines, transport system and their function time-lapse microscopy, protein (Baumann et al. bioRxiv, 2019). To further biochemistry, as well as genetic understand which different mRNA techniques.” transport pathways exist, the Maurer Lab References: develops new high-throughput protein- protein and protein-RNA interaction 1. Burga, A., Casanueva, O., and Lehner, assays (Yang et al. Nature B. Nature, 480, 250-253 (2011) Communications, 2018). 2. Casanueva, O., Burga, A., and Lehner, B. Science, 335, 82-85 (2012) The project the successful candidate will Keywords. epigenetic inheritance, C. work on is based on a validated result elegans from our high-throughput protein interaction screen. We identified a new link between a nuclear mRNA transport
Master of Multidisciplinary Research in Experimental Sciences Major Research Projects BIST-UPF 2020/2021 factor and different motor proteins. The memory formation. How motor proteins candidate will work with a PhD student in such as kinesins and dynein recognise the lab to characterise these new their mRNA cargo and transport them to interactions with pure proteins and RNAs their destination is not understood. The to understand how they interact and Maurer lab develops new single-molecule assemble into functional complexes. To assays in microfluidic chambers to this end, the student will learn how to assemble neuronal mRNA transport design recombinant protein expression complexes from purified components. constructs, how to purify proteins with Through this approach, the Maurer Lab 17 different techniques and how to recently revealed the essential building fluorescently tag proteins. Furthermore, blocks of a minimal mammalian mRNA the student will be trained in bioanalytical transport system and their function techniques to quantify affinities between (Baumann et al. bioRxiv, 2019). To further proteins and proteins and RNAs. Finally, if understand which different mRNA time permits, the student will learn how to transport pathways exist, the Maurer Lab design and conduct Total-Internal- develops new high-throughput (HT) Reflection-Microscopy (TIRF-M) coupled in protein-protein and protein-RNA vitro reconstitution experiments to analyse interaction assays (Yang et al. Nature the function of purified factors during Communications, 2018). mRNA transport. The successful candidate will help to Keywords. Neuronal mRNA localisation, design new approaches to reveal which motor proteins, RNA binding proteins, different mRNA transport pathways exists single-molecule microscopy, biophysics in induced mammalian neurons. To this end, the student will work closely together with a PhD student and use CRISPR-Cas9 CRG-2004. Understanding the molecular to create cell lines with degron-tagged basis for bidirectional neuronal mRNA candidate proteins, which were detected transport as potential mRNA-cargo adapters by our HT-screening approaches. To enable live cell imaging of mRNA transport dynamics, Supervisor. Sebastian Maurer the student will further validate molecular Research group. Cytoskeleton dependent beacons on in vitro transcribed mRNAs RNA localisation mechanisms and help to implement mRNA live-imaging protocols. If time permits, the project Project Description. The Maurer Lab further foresees to generate photo- wants to understand the biochemical cleavable motor proteins which have to be processes that drive the generation of first validated in vitro before they will be neuronal mRNA distributions. Thousands used as a tool in induced neurons to test of mRNAs are transported into axons and which motor are responsible for axonal or dendrites and their local translation at the dendritic mRNA localisation. right location is important for neuron development, polarization and synaptic Keywords. Neuronal mRNA localisation, plasticity which underlies long-term live cell imaging, protein and RNA
biochemistry, auxin-induced degrons, Besides adding a piece to the X- photo-inactivation reactivation puzzle, the student will be immersed within a young team inside a dynamic international research CRG-2005. X-chromosome reactivation environment at CRG, which will help in iPSCs and mouse embryos her/him to gain skills furthering his/her scientific career. Supervisor. Bernhard Payer Keywords. Pluripotency, Epigenetics, iPSC- reprogramming, X-chromosome Research group. Epigenetic reactivation Reprogramming in Embryogenesis and the Germline Project Description. In our lab, we are studying how epigenetic information is CRG-2006. Epigenetic reprogramming in erased during mammalian development. mammalian germ cells In particular, we study epigenetic reprogramming of the X-chromosome in mouse embryos, induced pluripotent stem Supervisor. Bernhard Payer cell (iPSC) and in the germ cell lineage in Research group. Epigenetic vivo and in vitro. Using a multidisciplinary Reprogramming in Embryogenesis and approach, we want to gain insight into the Germline how epigenetic reprogramming is linked to its biological context, with long-term Project Description. In our lab, we are implications for regenerative and studying how epigenetic information is reproductive medicine. erased during mammalian development. In particular, we study epigenetic In this project, the prospective student reprogramming of the X-chromosome in would study the function of candidate mouse embryos, induced pluripotent stem factors for X-chromosome reactivation in cell (iPSC) and in the germ cell lineage in iPSCs and early mouse embryos. The vivo and in vitro. Using a multidisciplinary project will involve iPSCs reprogramming approach, we want to gain insight into and monitoring X-chromosome activity how epigenetic reprogramming is linked using an XGFP-reporter. Using knockdown to its biological context, with long-term and/or CRISPR deletion, the mechanism implications for regenerative and will be studied, by which the candidate reproductive medicine. acts on epigenetic reprogramming and at which stage X-reactivation is affected. The In this project, the student would work with student will learn a number of methods germ cells from mouse embryos and/or including iPSC reprogramming, shRNA differentiated in vitro from embryonic stem knockdown, FACS analysis, cells (ESCs). The in vitro approach has the immunohistochemistry, RNA-FISH, qPCR, advantage of providing more material etc. and being more amenable to perturbation. On the other hand, germ
Master of Multidisciplinary Research in Experimental Sciences Major Research Projects BIST-UPF 2020/2021 cells from embryos can provide the tackle this complexity, we incorporate accurate biological context for testing the techniques from a wide range of fields-- applicability of our findings from the in molecular genetics, reliability engineering, vitro system. Momentarily, we use this two- bioinformatics, statistical physics, survival system strategy to elucidate the signals analysis, high-throughput imaging, and and mechanisms responsible for X- stochastic modelling. Focusing on reactivation in mouse and human germ C.elegans as a model system, we seek to cells. develop experimental and computational methods in parallel to help us characterize Besides adding a piece to the X- 19 where, when, and why aging occurs, and reactivation puzzle, the student will be how we might effectively intervene in its immersed within a young team inside a progression. dynamic international research environment at CRG, which will help Objectives: contribute to the development her/him to gain skills furthering his/her of our high-throughput imaging technology scientific career. Training outcomes: learn how to work with a complex experimental apparatus Keywords. Keywords: Germ cells, involving hardware, software, and Epigenetics, X-chromosome reactivation, biological components. reproduction. Keywords. Aging, microscopy, stochastic CRG-2007. Dynamics of Living Systems processes Supervisor. Nicholas Stroustrup Research group. Dynamics of Living Systems Project Description. Our research group seeks to link the macroscopic symptoms of aging to their molecular origins. In aging, a variety of mechanisms contribute at short, medium, and longtime scales. Furthermore, aging appears to involve a substantial degree of random chance. To
INSTITUTE FOR BIOENGINEERING OF CATALONIA (IBEC) IBEC-2001.Nanoprobes & Nanoswitches I analyze receptors, ion channels and synaptic networks in the brain. These tools Supervisor. Pau Gorostiza are synthetic compounds with a double Research group. Nanoprobes & functionality: They are pharmacologically Nanoswitches active, binding specifically to certain proteins and altering their function, and Project description. One of the group’s they do so in a light-regulated manner that research lines is focused on developing is built in the same compound usually by nanoscale tools to study biological means of photoisomerizable azobenzene systems. These tools include groups. Recent projects in this area instrumentation based on proximity include the development of light-regulated probes, such as electrochemical tunneling peptide inhibitors of endocytosis named microscopy and spectroscopy (ECSTM, TrafficLights and the synthesis of small ECTS), atomic force microscopy (ECAFM) molecule photochromic inhibitors to and single molecule force spectroscopy manipulate several G protein-coupled (SMFS) that we apply to investigate receptors like adenosine A2aR and electron transfer in metal oxides and metabotropic glutamate receptors mGlu5. individual redox proteins. These studies In addition, some of these light-regulated are relevant to the development of ligands also bear an additional biosensors and molecular electronics functionality: a reactive group for covalent devices. Recent advances include the conjugation to a target protein. Examples following projects: methods for nanoscale include a photochromic allosteric conductance imaging under regulator of the G protein-couple receptor electrochemical control, measurement of mGlu4 that binds irreversibly to this the nanomechanical stability and electron protein and allows photocontrolling its transfer distance decay constants of activity in a mouse model of chronic pain individual redox proteins. Based on our and a targeted covalent photoswitch of development of nanoscale field-effect the kainate receptor-channel GluK1 that transistors using redox proteins, we have enables photosensitization of recently published a method to measure degenerated retina in a mouse model of conductance switching in proteins “wired” blindness. We also demonstrated for the between two electrodes and their current- first time two-photon stimulation of neurons voltage characteristics. and astrocytes with azobenzene-based The objective of the research line on photoswitches. nanoswitches is to develop molecular Students can expect to learn the relevant switches that are regulated with light in techniques for the proposed project in one order to manipulate and functionally of the research lines (from
Master of Multidisciplinary Research in Experimental Sciences Major Research Projects BIST-UPF 2020/2021 electrochemistry to scanning probe conditions that allow for an effective microscopies and surface protein-protein ET. We use scanning probe functionalization; from synthetic chemistry microscopies, SPMs (scanning tunneling to electrophysiology and fluorescence and atomic force microscopies and imaging, in vitro and in vivo) and to work spectroscopies -STM and AFM-), to independently within a team of highly evaluate immobilized proteins under multidisciplinary and motivated electrochemical control. researchers. The student will perform studies at the Keywords. electrochemistry, redox nanoscale using SPMs to measure ET 21 proteins, photosynthetic complexes, currents and interaction forces between optogenetics, photopharmacology partner proteins, under controlled environmental and biologically relevant conditions (electrochemical potential, IBEC-2002. Nanoprobes & Nanoswitches temperature, pH, ionic environment). The II student will learn to work with SPMs but also on protein immobilization protocols, surface functionalization, electrochemical Supervisor. Pau Gorostiza studies. He/she will also learn on Research group. Nanoprobes & bibliographic search, data treatment and Nanoswitches presentation (written and oral) of the results. The student will incorporate to the Project description. Protein mediated Nanoprobes & Nanoswithces research electron transfer (ET) is essential in many group and will actively participate in the biological processes, like cellular meetings and discussions. He/she will respiration or photosynthesis. The acquire basic competences related to the exceptional efficacy of these processes is experimental work in a multidisciplinary based on the maximization of lab on nanobiotechnology. donor/acceptor coupling and the optimization of the reorganization energy. Keywords. Proteins; electron transport; scanning probe microscopies; single Single molecule techniques can provide molecule; interactions 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
IBEC-2003. Nanoprobes & Nanoswitches properties of model membranes, including III the presence of glycosphingolipids related to specific pathologies, and associate them to their role processes at Supervisor. Pau Gorostiza the cellular level. The student will be Research group. Nanoprobes & involved in the design and building of Nanoswitches supported lipid membranes, and their characterization using force spectroscopy Project description. Cell processes like (indentation and tube-pulling) based on endocytosis, membrane resealing, AFM. The student will be trained on lipid signaling and transcription, involve vesicles and membranes preparation, conformational changes which depend on surfaces functionalization, and to work the chemical composition and the with SPMs techniques. He/she will also physicochemical properties of the lipid learn on bibliographic search, data membrane. These properties are directly treatment and presentation (written and related to the lateral packing and oral) of the results. The student will interactions at the molecular level, that incorporate to the Nanoprobes & govern the membrane structure and Nonsnitches research group and will segregation into nano (or micro) domains. actively participate in the meetings and The better understanding of the discussions. He/she will acquire basic mechanical role of the lipids in cell competences related to the experimental membrane force-triggered and sensing work in a multidisciplinary lab on mechanisms has recently become the nanobiotechnology. focus of attention. The local and dynamic nature of such cell processes requires Keywords. lipid membrane; biophysics; observations at high spatial resolution. atomic force microscopy; force Atomic force microscopy (AFM) is widely spectroscopy; nanomechanics used to study the mechanical properties of supported lipid bilayers (SLBs). We investigate the physicochemical and structural properties of lipid membranes IBEC-2004. Improving site-specific combining AFM and force spectroscopy targeting of nanomedicines for (AFM-FS) under environmentally controlled treatment of lung or brain diseases conditions. We use simplified model Supervisor. Silvia Muro membranes including several lipid representatives of mammalian or Research group. Targeted bacterial cells. We also study the Nanotherapeutics and Nanodevices mechanical properties of lipid Project description. Novel drug membranes from nanovesicles with nanocarriers improve the solubility, technological applications, like drug biodistribution, and overall performance delivery. and safety of therapeutic agents. Their The general goal is to assess the structure, functionalization with targeting moieties phase behavior and nanomechanical enables site-specific drug delivery to
Master of Multidisciplinary Research in Experimental Sciences Major Research Projects BIST-UPF 2020/2021 selected cells. Although this paradigm is process of designing, executing, recording easily achieved in cell mono-culture and reporting of research, oral and written models, in vivo specificity of targeted communication skills, authorship if vehicles remains a challenge. The publishable results are used for complexity of the physiological conference presentations or article environment within the body and its submissions, and overall participation in a diversity in cellular phenotypes contribute stimulating, interdisciplinary and to this. The project will focus on examining innovative research program. specific targeting of nanocarriers in Keywords: Drug delivery, nanocarriers, 23 complex and physiologically relevant co- site-specific targeting, multicellular culture models, providing guidance for models, lung or brain disease future design of nanomedicines. This will be examined for one of two relevant organs: (1) the brain, a part of the central IBEC-2005. Development of nervous system very difficult to reach from computational Solutions for Ion Mobility the circulation due to the blood-brain Spectrometry Data Analysis barrier, vs. (2) the lung, a peripheral organ which receives full cardiac output after i.v. injection. Different diseases affecting each Supervisor. Santiago Marco organ require targeting drugs to particular Research group. Signal and Information cell types, but not all, for which the project Processing for Sensing Systems will broadly help design more precise systems for efficiency and safe treatment. Project Description. In the group we Three aims will be encompassed, develop full computational workflows for including (a) biological characterization a the analysis of metabolomics data based new co-culture cell model, (b) synthesis on NMR, GC-MS or LC-MS techniques. Gas and characterization of targeted Chromatography-Ion Mobility nanocarriers, and (c) examination of the Spectrometry is a novel technique for the specific interaction of said nanocarriers analysis of the volatile fraction of the with said co-culture models vs. more metabolome. Based on previous research classical systems. Techniques to be used at the group, the main aim is to produce include solvent-evaporation methods for an R-package that integrates basic GC- polymer nanoparticle synthesis, dynamic IMS signal processing. The student will get light scattering, electrophoretic mobility training in signal processing in the R and electron microscopy for nanoparticle technology and in the development of size/shape and surface charge, human software packages. cell culture and fluorescence microscopy Keywords. Data Analysis, Signal to visualize nanoparticle-cell interactions, Processing, R language, Metabolomics and image analysis algorithms for semiquantitative measurements. Additional experiences to be gained include training on research safety and ethical conduct, participation in the
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