EDBB Open Positions

This page will be updated more often as we enter the Spring of 2020 and as the EDBB program will be informed of new positions becoming available for the June 17-19, 2020 Hiring Days event at EPFL. Meanwhile, do not hesitate to contact the laboratories which interest you to find out whether they have upcoming openings for PhD students.

Exploring patterns of surface proteins on the cell membrane using selective-binding with DNA precision particles. 

We will exploit multivalency of rigid nanoparticles to achieve selective cell binding and characterise (dynamic) protein patterns on the cell surface. 

Insights can be used for diagnostics as well as understand and manipulate cell-adhesion and surface signalling pathways.

We offer the following PhD position on the ecology and evolution of bacterial pathogens.

Pathogen frequently emerge due to their adaptation to natural environments or non-human hosts. Within this context, bacteria often engage in interbacterial competition and cooperation. Our lab studies these interbacterial interactions at the mechanistic level using microbial cell biology, genetics, and basic biochemistry and we offer a PhD position on these aspects.

We offer the following interdisciplinary PhD (iPhD) position that will focus on bacterial shape determinants:

Despite unusual bacterial shapes and shape transitions having been documented over centuries, the underlying functionality has remained largely enigmatic. Our project will address this knowledge gap by combining quantitative shape measurements based on advanced microscopy techniques with optimal shape modeling followed by phenotypic testing of genetically engineered shape-transitional or shape-locked bacteria. Our model bacterium for this study will be Vibrio cholerae

The PhD student will be trained in both laboratories and apply his/her acquired skills to this interdisciplinary project.

PhD project no. 1:

Characterization of spatiotemporal organization of the brain lipidome

Neural cells produce thousands of different lipids, each endowed with peculiar

structural features and contributing to specific biological functions. Lipid composition

affects neuron firing properties influencing vesicle fusion and fission processes,

membrane conductivity, and ion fluxes. Nonetheless, a systematic and fine-grained

characterization of lipid composition in the different brain regions is not available.

Lipids also play a fundamental role in brain development. For example, some lipids,

such as glycosphingolipids, mediate cell-cell recognition, others like steroid hormones,

and phosphoinositides, have a role in stimulating cell growth and signaling.

Furthermore, exposure to teratogenic agents, during development, is associated to

cognitive or sensory impairments that might be mediated by interference of these

teratogens with lipid biogenesis and metabolism. However, little is known about how

the regional specificity of lipids is developmentally established and maintained

throughout adulthood.

The doctoral candidate will aim at filling this gap by collecting systematic data

necessary to construct a high spatially resolved atlas of the lipidome of the adult and

developing mouse brain. We expect this resource to provide numerous cues of the

underlying regulation mechanisms; the most interesting observations will be

experimentally followed up by the candidate and related to function.

The project offered jointly by the La Manno and D’Angelo labs will allow the candidate

to:

– Use super-resolved Imaging Mass Spectrometry (IMS) to reconstruct the spatial

lipidome in serial brain sections from adult and developing mice.

– Assess the lipid deregulation resulting from the exposure of different teratogenic

conditions.

– Investigate the relation between the lipidome of different stem cell populations and

their neural progeny.

– Investigate how perturbation to genes involved in lipid metabolism affects brain development.

– Assess how direct perturbations of lipid composition affect morphogenesis and adult brain structure and composition.

PhD project no 2:

Construction and analysis of a Lipid Brain Atlas

Single-cell and spatial transcriptomics technologies have matured significantly in the

last few years and are now extensively used to build comprehensive atlases of tissue

gene expression heterogeneity. However, while datasets of this kind are accumulating,

similar resources that describe biochemical heterogeneity of tissues are still lacking.

With the advent of super-resolved Imaging Mass Spectrometry, it is now possible to

efficiently and rapidly measure the biochemical composition of tissues at micronresolution.

Using the technique, the laboratories of Giovanni D’Angelo and Gioele La

Manno have recently found a substantial spatial organization of lipids in the brain, the

regional specificity found was significantly more extensive than previously believed.

In the brain, the role of lipids is crucial for different functions; for example, it

contributes to setting neuron firing properties, controls membrane conductivity and ion

fluxes. Analyzing this unexplored heterogeneity is likely to reveal new biochemical

processes and principles that characterize different neurons and brain areas. Our labs

are actively working to collect an extensive dataset to build a resource that will serve

as a powerful tool for neurochemical research.

The doctoral candidate will have a central role in this effort. She/he will develop new

computational methods to process, analyze, and organize this extensive dataset. We

expect the candidate to:

– Develop ad-hoc machine learning algorithms (e.g., latent variable decomposition,

deconvolution approaches) for the analysis and interpretation of spatial lipidomic data.

– Use the tools developed to analyze the regional heterogeneity of the mouse brain

lipidome.

– Organize this knowledge into a resource for the community.

– Construct a volumetric 3d model of the brain and register all the data obtained in this

reference frame.

– Integrate the lipid atlas with gene expression brain atlases and build principled models that can predict one data type from the other.

One or two EDBB PhD positions are offered with a choice among the following three projects:

  1. Dissecting de novo centriole assembly mechanisms.

Background

Centrioles are small organelles that are critical for forming cilia, and which exhibit a striking 9-fold radial symmetric arrangement of microtubules. In proliferating cells, centrioles assemble once per cell cycle next to an existing centriole, although centrioles can assemble de novo in some circumstances. We discovered components that are essential for the onset of centriole assembly across evolution. We deploy a multidisciplinary approach to uncover the principles by which these components govern organelle biogenesis.

Objectives

Determine the sequential recruitment and the requirement of centriolar proteins during de novo assembly in cultured human cells. Investigate whether de novo assembly involves a phase separation mechanism and repurpose a high-speed atomic force microscopy (HS-AFM) assay to probe de novo organelle biogenesis. Moreover, investigate de novo centriole formation in the physiological setting of the water fern or of Naegleria.

Approaches

Molecular biology, including CRISPR/Cas9 genome engineering, cell biology, live cell imaging, super-resolution microscopy (STORM, iSIM, Ux-EM-STED), cryo-electron microscopy, high-speed atomic force microscopy (HS-AFM), proteomics.

  1. Engineering SAS-6 proteins to decipher centriole assembly mechanisms

Background

Centrioles are small organelles that are critical for forming cilia, and which exhibit a striking 9-fold radial symmetric arrangement of microtubules. In proliferating cells, centrioles assemble once per cell cycle next to an existing centriole and near orthogonal to it. We discovered that the evolutionarily conserved SAS-6 proteins self-assemble into 9-fold radially symmetric structures thought to template the formation of the entire organelle.

Objectives

Engineer SAS-6 proteins to probe the mechanisms governing centriole assembly. This includes protein modification to alter the symmetry and the diameter of the centriole in human cultured cells. Moreover, chimera will be generated between SASA-6 proteins from different species to probe the underlying self-assembly mechanisms. Furthermore, SAS-6 proteins will be repositioned in human cultured cells to assay whether their geometry is key for imparting orthogonal assembly.

Approaches

Protein modeling, molecular biology, including CRISPR/Cas9 genome engineering, cell biology, live cell imaging, super-resolution microscopy (STORM, iSIM, Ux-EM-STED), electron microscopy.

 

  1. Dissecting Cep135/Bld10p function in centriole assembly

Background

Centrioles are small organelles that are critical for forming cilia, and which exhibit a striking 9-fold radial symmetric arrangement of microtubules. In proliferating cells, centrioles assemble once per cell cycle next to an existing centriole, although centrioles can assemble de novo in some circumstances. We discovered components that are essential for the onset of centriole assembly across evolution. We deploy a multidisciplinary approach to uncover the principles by which these components govern organelle biogenesis.

Objectives

Discover mechanisms through which proteins located at the centriole periphery contribute to organelle biogenesis, both in proliferating cells and in a de novo setting. An initial emphasis will be on dissecting the function of Cep135/Bld10p.

Approaches

Molecular biology, including CRISPR/Cas9 genome engineering, cell biology, live cell imaging, super-resolution microscopy (STORM, iSIM, Ux-EM-STED), structural biology, cryo-electron microscopy, high-speed atomic force microscopy (HS-AFM).

PhD position in hyperpolarized MRI molecular imaging
Hyperpolarized carbon-13 MRI is a novel molecular imaging technique capable to enhance MRI sensitivity thus enabling to monitor in real-time function, perfusion and metabolism using injected substrates. This Ph.D. thesis will focus on molecular imaging of hyperpolarized glucose for monitoring brain metabolism in real-time. The project involves developing and optimizing hyperpolarized MRI tools and implementing them in vivo in healthy rodents and disease models.
The laboratory of function and metabolic imaging (LIFMET), is equipped with two unique custom-designed hyperpolarization instruments (7 tesla and 5 tesla polarizers operating at 1K). These systems enable to push the sensitivity limits of HP MRI beyond what is feasible with commercial instrumentation. The project benefits from the CIBM platform including highly qualified technical staff composed of engineers and trained veterinarians.
The application including a motivation letter, the CV and two reference letters should be sent by email to:

[email protected]  and [email protected]

PhD candidates will be enrolled in an EPFL PhD program such as EDBB, EDPY, or EDEE.
For more information, you can contact Prof. Rolf Gruetter and/or Dr. Mor Mishkovsky

Neurodegenerative Disease under the Microscope: A Multimodal Imaging Approach to Decipher Aggregation Networks using Huntington Inclusion Formation as a Model System

This joint interdisciplinary PhD project exploits synergies between the Lashuel laboratory (SV-BMI-LMNN) and the Radenovic laboratory (STI-IBI-LBEN). Research in LMNN focuses on applying chemistry and biology approaches to elucidate the mechanisms of protein misfolding and aggregation and their contribution to neurodegenerative diseases. LBEN works in the research field that can be termed single molecule biophysics. They develop techniques and methodologies based on optical imaging, biosensing and single molecule manipulation with the aim to monitor the behavior of individual biological molecules and complexes in vitro and in live cells.

Neurodegenerative diseases such as Alzheimer’s or Huntington’s disease (HD) pose one of the grand challenges for our society. They severely impact the quality of life; there is no cure and therapies only alleviate the symptoms. Recent evidence suggests that phase separation and subsequent phase transitions play a key role in protein aggregation of intrinsically disordered proteins such as Huntingtin. However, very little is known about molecular and cellular determinants of these transitions. We believe that the combination of unique expertise, biochemical tools to manipulate Htt structure and PTMs, and novel imaging modalities position us well to make progress that has great potential to address this knowledge gap and develop novel approach with wide-ranging applications in basic and translational neurodegenerative research. Towards this goal, we will apply single-molecule fluorescence super-resolution (localization microscopy, single particle tracking), phase microscopy and image analysis (deep learning) to directly study Huntington’s disease in cellular and neuronal HD model systems that are well characterized at the biochemical, biophysical, omics and ultrastructural levels. The project connects the expertise of the Radenovic lab in imaging technologies with the extensive know-how of neurodegenerative disease of the Lashuel Lab.

We seek highly talented, enthusiastic and exceptionally motivated candidates with a M.Sc. degree in (bio)physics with an affinity for (neuro)biology and biophysical chemistry. We also encourage candidates with a background in (neuro)biology with an interest in advanced microscopy to apply for this position.
Good communication skills and team spirit are important. Fluency in English is an absolute requirement; the candidate must be conversant and articulate in English speaking and should have strong writing skills. An interview and a scientific presentation will be part of the selection process.

The qualified candidate will benefit from working in a collaboration of two very dynamic and multidisciplinary groups in a highly collaborative and stimulating environment and will have access to state of the art laboratories and core-facilities and a competitive salary. For more information about the labs, please visit our websites and review our recent publications at:

The Lashuel laboratory: https://www.epfl.ch/labs/lashuel-lab/

The Radenovic laboratory: https://www.epfl.ch/labs/lben/

We’re always looking for talented PhD students. with following background : optics, electronics, optical and magnetic trapping, cell and molecular biology, polymer physics, nanotechnology, and clean room experience.

Engineering organoid morphogenesis

Organoids form through poorly understood morphogenetic processes in which initially homogeneous ensembles of stem cells spontaneously self-organize in suspension or within permissive three-dimensional extracellular matrices. Yet, the absence of virtually any predefined patterning influences such as morphogen gradients or mechanical cues results in an extensive heterogeneity. Moreover, the current mismatch in shape, size and lifespan between native organs and their in vitro counterparts hinders their even wider applicability. We have two openings at the PhD level to develop next-generation organoids that are assembled by guiding stem cell self-patterning through engineered microenvironments (1). One PhD project will focus on human gastrointestinal organoids (2), another one on embryonic organoids (3).

  • Brassard, J.A., Lutolf, M.P., Engineering Stem Cell Self-organization to Build Better Organoids, Cell Stem Cell, 24 (6), 860-876 (2019)
  • Gjorevski, N., Sachs, N., Manfrin, A., Giger, S., Bragina, M.E., Ordonez-Moran, P., Clevers, H., Lutolf, M.P., Designer matrices for intestinal stem cell and organoid culture, Nature, 539, 560-564 (2016)

Beccari, L., Moris, N., Girgin, M., Turner, D.A., Baillie-Johnson, P., Cossy, A.C., Lutolf, M.P., Duboule, D., Martinez Arias, A., Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids, Nature, 562 (7726), 272 (2018)

We expect to hire 1 PhD students in 2020 in the area of cell-free synthetic biology / synthetic cell engineering.

Control of genetic oscillators in embryonic development

The Oates group studies the development of body segments using the zebrafish embryo as a model system. This involves a population of genetic oscillators that generate a collective rhythm and spatial wave patterns. The pulse of this “segmentation clock” governs the generation of each new body segment, and its failure causes the birth defects of congenital scoliosis. Our lab uses techniques including genetic engineering, microfluidics, optogenetics, time-lapse imaging, image processing, physical modeling and old-fashioned embryology. We are currently looking for someone to work on the development and/or analysis of new transgenic reporter systems that allow us to probe the dynamics of gene expression in real time within the developing embryo, with the aim to understand what controls the fundamental period of the system. Other ideas are welcome too! This person will get to work in a lively interdisciplinary team and will need to be motivated and independent.

We are looking for a student to run a multidisciplinary project at the interface of soft robotics and biophysics. The goal of the project is to develop mechanically actuated systems to understand how bacterial pathogens physically interact with their environments.

The Suter lab is interested in quantitative analysis of gene expression to understand how cell identities are established and maintained. The PhD project we propose aims at quantitative, biophysical characterization of the transcription factor network that controls the identity of embryonic stem cells. It will involve cutting edge approaches such as genome editing, quantitative live cell imaging and cell tracking, and single molecule imaging. This project is part of a Sinergia Consortium and will involve interdisciplinary collaboration with our partner labs experts in microfluidics and in vitro transcription factor characterization (Maerkl lab, EPFL), and computational modelling of biological networks (van Nimwegen lab, University of Basel).

We also propose a project to study the role of mitotic bookmarking in cancer stem cell self-renewal. Cancer stem cells are central to the fueling of tumorigenesis through their ability to self-renew. Over the past years, transcription factors binding to mitotic chromosomes have been suggested to play a role in the ability of stem cells to self-renew, but whether mitotic bookmarking plays a role in self-renewal of cancer stem cells is unknown. Here the candidate will explore the role of mitotic retention of oncogenic transcription factors in the ability of cancer stems cells to maintain their gene expression program over cell division. To tackle this question, the PhD candidate will learn and apply a broad set of approaches, such as live cell fluorescence microscopy, genomics approaches (ChIP-seq, CUT&RUN, ATAC-seq, RNA-seq), genome editing using CRISPR technology, optogenetics, and in vitro 3D culture and migration assays.

For more details, see web pages of the EDBB program’s potential thesis directors.