PhD positions

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Next Selection : February 9-10th 2021

Deadline for application: December 15th 2020

Application process

Programme flyer

 

The name of possible thesis directors can be found in the list of participating laboratories on our website.

 

For students interested in applying through the Track 2 procedure, they are encouraged to make a list of up to 5 choices, with the understanding that not all laboratories have open positions at a given time, and they may be considered  by other faculty members with similar interests.

 

The applications should to be sent to: cancerimmunology@unil.ch

OPEN POSITIONS:

Assistant Professor Manuele REBSAMEN, Department of Biochemistry, Epalinges

         PhD student position in pathogen sensing, innate immunity and autoimmunity

The Rebsamen lab investigates the signaling pathways and metabolic processes that allow immune cells to detect and respond to invading pathogens, and their implication in autoimmune diseases. A particular focus of the lab is the characterization of the role of Solute Carriers (SLCs), a family of transporter proteins, in immune functions and immunometabolism.

Detection of invading pathogens by the innate immune system is crucial to initiate antimicrobial programs and trigger appropriate immune adaptive responses. Innate sensing relies on the recognition of specific microbial molecules by a set of invariant receptors. Endolysosomal Toll-like receptors (TLR) 7,8 and 9 sense viral and bacterial-derived nucleic acids leading to the induction of antimicrobial genes and production of proinflammatory cytokines and type-I interferons. Importantly, aberrant activation of these pathways is associated with autoimmune conditions, such as systemic lupus erythematosus (SLE). Despite the relevance in both infectious and autoimmune diseases, the signaling pathways and the regulatory mechanisms controlling endolysosomal TLR function remain only partially understood. We recently discovered that the solute carrier SLC15A4 and the uncharacterized protein TASL, both encoded by SLE-associated genes, form a signaling complex required for endolysosomal TLR responses (1).

We are seeking an enthusiastic candidate who is interested in uncovering the molecular mechanisms and regulatory processes controlling innate immune responses, focusing in particular on the network controlling the SLC15A4/TASL/IRF5 pathway and its role in TLR signaling and autoimmunity. In order to achieve this, the successful applicant will employ state-of-the-art biochemical, molecular and cell biological approaches including proteomics and CRISPR/Cas9-based screening technologies.

         Selected publications (*first authors, # corresponding authors):

1. Heinz, …, Rebsamen# & Superti-Furga#. TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9. Nature. 2020;

2. Fauster*, Rebsamen*#, …, Superti-Furga#. Systematic genetic mapping of necroptosis identifies SLC39A7 as modulator of death receptor trafficking. Cell Death Differ. 2019;

3. Rebsamen, …, Superti-Furga. SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature. 2015;

For further information: manuele.rebsamen@unil.ch, Rebsamen lab

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Assistant Professor Alexis JOURDAIN, Department of Biochemistry, Epalinges

PhD Student Project: Discovering Novel Genetic and Metabolic Programs that Support Cellular Energy Production and Mitochondrial Plasticity

 

Mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis are the two major pathways for ATP production – or energy metabolism. The reliance on these pathways and the abundance and composition of mitochondria are known to differ across tissues and may vary during processes such as cellular differentiation and immune response. Shifts in the OXPHOS/glycolysis balance are also seen in pathologies such as cancer and metabolic syndromes (mitochondrial disorders). At present, the full set of molecular mechanisms that support and control mitochondrial biogenesis and energy metabolism is not known. Understanding how these programs function holds promise for diagnosis and therapies by pointing to vulnerabilities that could either be corrected to promote healthy metabolism and immune function or exploited to starve tumors.

 

Our group will open in April 2021 at the Department of Biochemistry, University of Lausanne (Switzerland). We are looking to hire a PhD student starting mid-2021 to study mitochondria and energy metabolism in cellular models of differentiation, immune activation (immunometabolism) or mitochondrial disorders. The student will learn and use large-scale systems biology technologies including genome-wide CRISPR/Cas9 screening, metabolomics and quantitative proteomics, as well as biochemistry and cell biology techniques, to discover novel mechanisms involved in mitochondrial biogenesis and energy metabolism in his/her model of choice.

 

Candidates with strong interests in mitochondria and cellular metabolism are encouraged to apply. The spoken language in the team will be English. Prior experience with cell biology, immunology or systems biology are a plus.

 

More info on the UNIL Jourdain lab web page, or by email to: alexis.jourdain@unil.ch

 

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Prof. Johanna Joyce

Department of Oncology, Ludwig Institute for Cancer Research, Lausanne

 

Objectives: Emerging evidence indicates that immune cells are mobilized and activated in the tumour microenvironment (TME) during metastatic cancer progression. The TME is also altered following various anti-cancer therapies, which can paradoxically contribute to a lack of response/ acquired resistance to treatment. In particular, inflammation can promote metastatic progression. We will systematically focus on different immune cell types whose levels vary across systemic inflammation, in specific tissues - including the brain, and whose variations are further exacerbated by the presence of a primary tumour. We will determine whether this translates to increased cancer metastasis to this site, and the potential dependency on specific cytokines or factors. Subsequent genetic, chemical or biological studies will follow to confirm the causality of these mechanisms to the metastatic phenotype. The underlying mechanistic contribution of the microenvironment to metastasis and therapeutic resistance will be based on a range of complementary techniques including mouse models of cancer, 3D co-culture systems, computational approaches, and analysis of patient samples in collaboration with our clinical colleagues.

 

Additional training opportunities: This project will be embedded within a metastasis-focused training network - Evomet. Evomet is funded by an EU-MSCA International Training Network grant, which includes labs across Europe. This is an excellent opportunity for an enthusiastic and motivated student to join the Lausanne site of the Evomet ITN, and to be part of this larger network with many training, research and education opportunities across the different locations. Applications are welcome from all over the world, but must not have resided in the host country (Switzerland in this case) during the previous 12 months, following the ITN directives to enhance international mobility of the student researchers.

 

For further information: www.joycelab.org, evomet-itn.eu

 

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Prof. Monika E. Hegi, PhD
Laboratory of Brain Tumor Biology and Genetics (LBGT)

Neurosurgery & Neuroscience Research Center
Department of Clinical Neurosciences, CHUV

Ch. Des Boveresses 155

CLE-C 306
CH-1066 Epalinges 

Switzerland

Phone 021 314 2582
Email: Monika.Hegi@chuv.ch

 

 

Project Proposal 2020

https://www.unil.ch/crn/en/home/menuinst/research-labs/brain-tumor-biology-and-genetics/monika-hegi.html

Targeting Pathway Vulnerabilities Induced by Epigenetic Disturbance in Glioblastoma

The laboratory works at the interphase of basic and clinical research in brain tumors. In the proposed project, we aim at identifying druggable vulnerabilities of cancer relevant pathways revealed upon disturbing the tumor cells by epigenetic drugs, such as Bromodomain inhibitors (BETi). BETi target chromatin readers such as BRD4 that regulate expression of proto-oncogenic genes. We have identified several gene signatures indicative of cancer relevant pathways that are disturbed upon treatment with BETi. Investigating the function of these genes/pathways mechanistically in in vitro models and with bio-informatics approaches, will inform on their suitability to serve, as targets for treatment and the biological function will guide the choice for the second drug to use. Hits will be tested for synergistic effects with BET inhibition. Successful combinations will be taken into patient derived orthotopic xenograft models in the mouse. Molecular biomarkers and magnetic resonance imaging/ spectroscopy based response markers will be developed for translation into the clinical setting. 1,2 3

References:

1. Gusyatiner O, Hegi ME. Glioma epigenetics: From subclassification to novel treatment options. Semin Cancer Biol. 2018; 51:50-58.

2. Gusyatiner O, Pham MDT, Lei Y, et al. BET inhibitors synergize with HDAC inhibitors and downregulate expression of interferon response genes in glioblastoma. In: AACR, ed. 109th Annual Meeting of the American Association for Cancer Research, Abstr #2923. Vol 78. Chicago, Illinois: AACR; 2018.

3. Stathis A, Bertoni F. BET proteins as targets for anticancer treatment. Cancer Discov. 2018; 8(1):24-36.

 

Ch. des Boveresses 155 - CP 51 - CH-1066 Epalinges
Switzerland
Tel. +41 21 692 57 00
Fax +41 21 692 57 05