EDBB Open Positions

This page will be updated starting in the Fall of 2019, as the EDBB program will be informed of new positions becoming available for the January 22-24, 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.

Our multidisciplinary lab, Bionanophotonic Systems Laboratory (BIOS) is at the cross-section of nanotechnology, photonics, biology and biochemistry. We are developing next generation biosensor and spectroscopy technologies enabling real-time, label-free and high-throughput analysis of low quantities of samples such as biomolecules, pathogens and live cells. Our technologies are aimed for numerous applications including disease diagnostics, point-of-care testing, drug discovery and fundamental biological studies. BIOS has world leading expertise in experimental nanophotonics (plasmonics, metamaterials), bioimaging, microfluidics and nanofabrication. We are looking for a motivated PhD student to join BIOS for developing cutting-edge biosensing devices and systems for impact real-world applications. Please check our most recent publications to get an idea about the ongoing projects:

  • Rapid and Digital Detection of Inflammatory Biomarkers Enabled by a Novel Portable Nanoplasmonic Imager. Small, https://doi.org/10.1002/smll.201906108 (2019).
  • Ultrasensitive Hyperspectral Imaging and Biodetection Enabled by Dielectric Metasurfaces. Nature Photonics 13 p. 390-396 (2019).
  • Imaging-Based Molecular Barcoding with Pixelated Dielectric Metasurfaces. Science 360, p. 1105-1109 (2018).
  • Resolving Molecule-Specific Information in Dynamic Lipid Membrane Processes with Multi-Resonant Infrared Metasurfaces. Nature Communications 9, p. 2160 (2018).
  • Label‐Free Optofluidic Nanobiosensor Enables Real‐Time Analysis of Single‐Cell Cytokine Secretion. Small 14, 1870119 (2018).

Engineering powerful proteins with novel functions for cell engineering, synthetic biology and therapeutic applications
Protein design has made tremendous progress in recent years and is becoming central to synthetic biology applications including cell engineering approaches. For example, engineered proteins with customized signaling responses to disease-associated molecules provide promising and powerful new therapeutic agents for cancer immunotherapy, regenerative medicine and autoimmune disorders.
Our lab is developing and applying computational-experimental protein design approaches for engineering proteins with a wide range of novel functions. The technologies have been validated on simple proof of concepts (e.g. Feng et al., Nat Chem Biol 2017; Arber et al., Curr Opin Biotech 2017; Keri et al., Curr Opin Struct Biol 2018; Young et al., PNAS 2018; Chen et al., Nat Chem Biol in press). Using these approaches, we now aim at designing innovative and powerful protein nanomachines towards engineering synthetic living cells or for improving the anti-tumor responses of engineered immune cells in cancer immunotherapies.
Specific projects typically involve some aspects of computational protein modeling and design using the techniques developed in the lab complemented by the directed evolution of desired protein functions and validation of engineered cells using a variety of
cell biology approaches. Collaboration with laboratories at the CHUV/UniL/Ludwig Institute for Cancer Research (e.g. Caroline Arber, George Coukos) are in place for testing engineered molecules and cells in mouse xenograft models before potential
translation to the clinic. Marrying empirical and computational protein engineering approaches has the unique potential to design a broad spectrum of cellular functions for engineering powerful cells with novel synthetic or sustained anti-tumor responses.

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.

In the laboratory for bio- and nano-instrumentation we focus on the development of new tools to study biological structures at the nanoscale. Our core technology is scanning probe microscopy, with special focus on high-speed atomic force microscopy (AFM) and scanning ion conductance microscopy (SICM). For the different applications in nanoscale biology (ranging from single molecule and single cell analysis all the way to tissue) we develop custom microscopes to address questions that are not solvable with existing tools. 

Project 1: Studying the molecular self assembly of centrioles using high-speed atomic force microscopy. Using our newly invented photothermal off-resonance tapping technique, you will record the self assembly of centrioles one molecule at a time. Since centrioles consist of many different molecules, you will develop tools for precise microfluidic handling of molecules into the AFM chamber. The large datasets recorded with HS-AFM require machine learning to extract the reaction kinetics at the single molecule level. This project is in collaboration with the cell and developmental biology laboratory of Pierre Gönczy. Key words: High-speed AFM, self assembly, microfluidics, image processing with machine learning

Project 2: AFM imaging inside living cells. AFM is intrinsically a surface measurement tool. Much of the interesting nanoscale biology however occurs on the inside of the cell. With the InCell  project we aim to change this, by developing a new find of atomic force microscope that can image inside living cells. This will be achieved through the combination of novel micro fabricated cantilevers, new AFM instrumentation, controls, and cellular biophysics. This project is a larger collaboration of 4 researchers in my lab and funded through an ERC consolidator grant. Keywords: micro fabrication, cell biology, biophysics, instrumentation, mechatronics.

Our laboratory (LNE) is a multidisciplinary environment promoting cross-fertilization among various expertise. We bring materials science, engineering, life science, and medicine together by the convergence of physicists, engineers, neuroscientists, and ophthalmologists cooperating to accomplish innovative projects. Our mission is the development of application-driven solutions based on compliant, minimally invasive, and replaceable neuroprosthetic devices. Ultimately, we aim at translating our research findings into clinical practice.

We are looking for a motivated student to join our laboratory and develop an innovative wireless photovoltaic neuroprosthesis for nerve stimulation. If you are looking for a phd in neurotechnology, working at the interface between polymer science, microengineering, and neuroscience then join our lab.

One EDBB PhD position is offered with a choice among the following three projects:

  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).

  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.

Role of post-translational modifications in modulating Htt aggregation and clearance

A PhD position in Neurosciences/Neurodegeneration is available in the Laboratory of Chemical Molecular Biology of Neurodegeneration (http://lashuellab.epfl.ch/) at the Swiss Federal Institute of Technology in Lausanne (EPFL), Switzerland (www.epfl.ch). The project is funded by the Marie Sklodowska-Curie Innovative Training Networks (MSC-ITN) under the European Commission’s Horizon 2020 programme – SAND: “Secretion and Autophagy and their roles in Neurodegneration”

Project description:

Our laboratory is working at the interface of chemical, molecular and cellular biology for discovery and validation of novel mechanisms and therapeutic targets for a variety of neurodegenerative diseases to develop novel targets for protein aggregation and clearance. The qualified candidate will work on a project to investigate the role of Huntingtin (HTT) protein post-translational modifications (PTMs) in its autophagy-mediated clearance using cellular and animal models of Huntington’s disease. Many studies suggest that autophagy enhancement can be one option to develop disease-modifying therapy for Huntington’s disease. Preliminary research from our group indicates that PTMs play a role in autophagy-mediated clearance of HTT. The project will explore the further the details of molecular mechanisms of HTT PTMs in mediating the autophagic clearance.

This PhD project will provide excellent inter-disciplinary and intersectoral research training to Early Stage Researchers (ESRs) in an emerging area of research with a close interaction from all SAND-MSC-ITN participating groups working on targeting a spectrum of diseases that is constantly rising worldwide.

Your profile:

We are looking for a highly motivated and enthusiastic person having finished or about to finish a Master`s degree and intending to obtain a Ph.D. in chemical biology of neuroscience. Excellent writing, communication skills and team spirit are essential. Prior experience in one or more of the following is highly recommended, but not required: use of models of neurodegeneration (in vivo or in vitro), standard biochemical, cellular and molecular biology techniques including cell culture, western blotting, transfection, transduction, light and electron microscopy, high-resolution microscopy, live cell imaging, PCR, etc.

Additionally, candidates will be required to meet the Marie Skłodowska-Curie Early Stage Researcher eligibility criteria: (http://ec.europa.eu/research/mariecurieactions/). At the time of appointment, candidates must have had less than four years full-time equivalent research experience and must not have already obtained a PhD. Additionally, they must not have resided in the host country for more than 12 months in the three years immediately before the appointment.

What we offer:

  • Very dynamic, multidisciplinary and a highly collaborative research group with a stimulating environment.
  • Access to state-of-the-art laboratories and core-facilities.
  • A competitive salary.
  • MSC-ITN fellowship being one of the most prestigious fellowships in Europe, gives a unique training program with its regular network meetings where you will meet experts in your field. You will be travelling to stay for a few months outside the host laboratory to do your secondments with project partners which give a great possibility to exchange knowledge and learn more on your topic.

For more information about our group, please visit our websites and review our recent publications at:

http://www.ncbi.nlm.nih.gov/pubmed/?term=Lashuel The Lashuel Laboratory: http://lashuellab.epfl.ch/ Brain Mind Institute : https://sv.epfl.ch/BMI

School of Life Sciences: http://sv.epfl.ch

 Application / Contact:

Interested applicants should submit a letter of interest, curriculum vitae and the names and addresses of three references to Ms. Marie Rodriguez [email protected]  EPFL SV BMI LMNN, AI 2149 Station 19 , CH1015 Lausanne.

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).

  1. Brassard, J.A., Lutolf, M.P., Engineering Stem Cell Self-organization to Build Better Organoids, Cell Stem Cell, 24 (6), 860-876 (2019)
  2. 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)
  3. 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)

Two Positions available in the areas of cell-free synthetic biology and transcriptional regulatory network / transcription factor engineering.

Our laboratory (LBMM) develops and applies microfluidic technology with a strong translational focus. The group’s ultimate goal is to establish novel treatments against cancer.

During the past couple of years we have established powerful microfluidic platforms for cell-based and biochemical assays. We continuously develop novel microfluidic chips, detection systems and software (mainly LabVIEW) for the discovery of new drugs and antibodies, partially in collaboration with large pharma industry. Furthermore, we use microfluidic technology to predict optimal (personalised) drug cocktails for cancer therapy. The group is very interdisciplinary and includes people with various backgrounds, including biologists, engineers and programmers. However, prior knowledge in microfluidics is not mandatory for joining!

Having a comprehensive microfluidic toolbox at hand (and expanding it continuously), we are now focusing on applications in three different research fields:

Therapeutic antibodies and T-cells: Droplet based microfluidics enables to screen a large fraction of the murine and human immune repertoire in a single experiment (e.g. El Debs et al., PNAS 2012, Chaipan et al., Cell Chemical Biology 2017, Shembekar et al., Cell Reports 2018). We are actively exploiting this for novel therapeutic approaches and have founded a biotech startup company translating our results (www.velabs-therapeutics.com).

Personalised medicine: We use microfluidic devices to test drug combinations directly on solid human tumor samples and to predict optimal therapies (e.g. Eduati et al., Nature Communications 2018). Current efforts focus on genetic and imaging-based readouts. In parallel, we are constructing next generation instruments for first clinical trials.

Genomics: We are actively developing microfluidic modules for single-cell barcoding and sequencing. This will enable the study of the mechanisms of drug resistance in great detail.

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. This person will get to work in a lively interdisciplinary team and will need to be motivated and independent.

Severe airway obstruction at different levels of the respiratory system may result from congenital or acquired instability of the tracheobronchial wall. Tracheomalacia commonly affects small children and is characterized by excessive airway collapse due to an exaggerated floppiness of the supporting cartilage. The treatment of tracheomalacia is complex, aiming to stabilize the central airways and no satisfactory solution has been developed so far. In this work, we propose to develop an innovative approach for the treatment of severe tracheomalacia in small children and to evaluate its performance in a physiologically relevant in vivo tracheomalacia model. In particular, we hypothesize that by restoring the physiological trachea shape with an extraluminal hydrogel-based splint thanks to the prestress present in the hydrogel, the collapsing of the ill-shaped trachea during the critical expiration phase of the respiratory cycle will be prevented. The project will therefore require competences in biomechanics and biomaterial (mostly hydrogel) development.

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/

Our laboratory is interested in dissecting the multifaceted connections between the gut and the liver in the enterohepatic system. Communication between both organs is accomplished by versatile signaling metabolites, such as bile acids, however, disruption of the tight regulation of their pool size and composition leads to metabolic disease and cancer. The project that we propose is strongly oriented toward the exploration of the role of these metabolites in the control of stem cell homeostasis and their impact on liver and colorectal cancer. Furthermore, a major focus will be the design of stem cell-based regenerative medicine approaches for liver metabolic diseases (non-alcoholic liver disease, aka NAFLD) that progress into liver cancer. The research will be performed using state-of-the-art in vivo approaches involving diet-induced and genetically modified animal models as well as mouse- and human-derived intestine and liver organoid cultures. These organoids will be used for environmental and genetic manipulation, imaging, co-cultures and scRNAseq to model metabolic disease and cancer, and used for high-throughput drug screening to identify therapeutic targets.

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.