Next Selection : FEBRUARY 8th & 9th 2022
Deadline for application : December 21th 2021
Margot Thome Miazza
Department of Biochemistry, UNIL
Chemin des Boveresses 155
Position : PhD-student (Funded by a newly awarded grant from the Swiss Cancer League)
Location: Department of Biochemistry
Field: lymphomagenesis, role of ubiquitin in immunity, deubiquitination.
Title: Understanding the role of MALT1-dependent cleavage of the tumor suppressor A20 in lymphomagenesis.
Project synopsis: Non-Hodgkin lymphoma (NHL) is the seventh most common cause of cancer and accounts for approximately 100,000 deaths per year in the US. Around 99% of NHL cases are T or B cell malignancies. Gaining new insight into aetiology and weaknesses of these diseases is thus highly impactful. Constitutive activation of the proto-oncogene MALT1 and inactivating mutations of the tumor suppressor A20 are well known hallmarks of a variety of these diseases. MALT1 is a protease that cleaves A20 at multiple sites, but the molecular consequences of A20 cleavage remain largely unknown. A20 is a multitalented enzyme: it acts as a deubiquitinating enzyme trimming K63-linked ubiquitin chains, but it also contains zinc finger (ZnF) motifs that can bind linear or K63-linked ubiquitin chains (via ZnF7) and conjugate K48-linked ubiquitin chains on selected protein targets (via ZnF4). It remains unknown how MALT1 activity impacts these different behaviors. This project will leverage the laboratory’s excellent reputation in the MALT1 field and further build on early interesting work from our laboratory, in which we identified protein targets that undergo opposing changes in ubiquitination status upon either MALT1 inhibition (which increases A20 levels) or A20 gene silencing. We will explore how altered ubiquitination of these targets controls lymphomagenesis. A better understanding of these mechanisms may provide useful diagnostic and therapeutic insights and identify novel targets for lymphoma therapy.
The Thome research group. We are a vibrant multidisciplinary laboratory that has mastered numerous cutting-edge skills across the spectrum of life sciences. With 20+ years of experience, we are also well established in this area, yet still keen to expand our repertoire of investigations. The student who is matched to this program will be enrolled in the PhD program in biochemistry in UNIL, which has a long history of creating top immunologists in both industry and academia. Aside from being integrated into a friendly, collaborative, and stimulating team, the student will also be given exciting opportunities to benefit from excellent in laboratory and classroom teaching, as well as gleaning top tips from external speakers and collaboration with local and international experts.
Prof. Michel Gilliet
Department of Dermatology, CHUV-UNIL
Field: AhR function, skin inflammation, skin inflammatory diseases.
Title: Dissecting the role of AhR in skin inflammation and the development of inflammatory skin diseases.
The aryl hydrocarbon receptor (AhR) is a transcription factor that regulates gene expression. AhR is activated by multiple endogenous indole derivatives and regulates immune responses, stem cell maintenance, and cellular differentiation. Using synthetic agonists and antagonists, the aim of this project is to define the role of AhR in skin inflammation and skin inflammatory diseases like psoriasis.
The research group
Prof. Michel Gilliet’s group has focused on the understanding of mechanisms that initiate and maintain inflammation in the skin. Over the past 15 years, our research has contributed to the field by several important discoveries:
We identified a new inflammatory pathway of the skin based on the dermal infiltration by plasmacytoid dendritic cells (pDC) and their activation to produce type I IFNs that is over-activated in psoriasis and lupus, where it drives chronic inflammation and disease initiation. This pathway is also activated in injured skin, but it is self-limited, providing a well-controlled initial inflammatory stimulus that promotes the wound healing response.
We have identified the factors that activate skin pDC and uncovered a fundamental function of cationic antimicrobial peptides (AMP) in the sensing of microbiota-derived nucleic acids released by AMP-killed commensal bacteria.
We discovered that some antimicrobial peptides including LL37 and Lysozyme not only trigger innate immune activation but also act as epidermal autoantigens targeted by autoimmune T cells in psoriasis. These AMP-specific autoimmune T cells produce Th17 cytokines which, on one hand, elicit the psoriatic phenotype and, on the other hand, sustain the antimicrobial peptide expression by keratinocytes, providing a feedback loop that perpetuates skin inflammation in psoriasis.
In Systemic Lupus Erythematosus (SLE), we demonstrated that circulating immune complexes are also composed of nucleic acid-antimicrobial peptide complexes. These pathogenic complexes originate from neutrophils undergoing extracellular traps (NET) formation leading to an exaggerated type I IFN production by pDC and the activation of autoimmune B cells producing antibodies directed against antimicrobial peptides.
The following profile is required for the successful candidate:
- Master degree in immunology, biology, biomedical sciences, biochemistry or a related discipline.
- Strong background in immunology and/or animal experimentation
- Ability to work independently as well as in a team
- Good English communication and writing skills
What we have to offer
- A challenging research project with prospects of high impact publications
- A dynamic multi-cultural scientific environment with interdisciplinary interactions and scientific meetings
- State of the art research facilities with spacious laboratories, cutting-edge technologies and expertise as well as large animal facilities and access to clinical samples
Faculty of Biology and Medicine, Rheumatology- CHUV
Avenue Pierre-Decker 4
Téléphone : 021 314 14 50
Position: PhD-Student (funded by the Swiss National Science Foundation (SNSF), project no. 320030_204524/1)
Location: Department of Musculoskeletal Medicine, Laboratory of Rheumatology (CHUV)
Field: Rheumatology, Osteoarthritis, Tendinitis, Pathologic calcification, Extracellular matrix.
Project: “The role of lysyl oxidases in musculoskeletal pathologic calcification”
Pathological calcification (PC) is the deposition of calcium-containing crystals in tissues that normally do not calcify and is a recognized cause for various diseases affecting musculoskeletal tissues, cardiovascular system, kidney and skin. It is a very common and disabling condition for which no resolutive therapies exist. Musculoskeletal PC, occurring in cartilage and tendons, is of etiologic importance in osteoarthritis and calcific tendinopathy respectively. The mechanisms involved in PC remain largely unknown. Collagens cross-linking, a post-translational modification of collagen fibers, supports physiological calcification of bones, but its role has never been described in the context of pathological calcification. Lysyl oxidases (LOX(L) are key enzymes catalyzing cross-linking between collagen molecules. Beside this classical role for which LOX(L) are known, additional extra and intracellular functions have been recently reported.
It is currently unknown if LOX(L) are relevant for PC, and whether functions other than collagen cross-linking mediate their putative effects. Overall, this project aims at elucidating whether LOX(L) could represent attractive new molecular targets for PC in osteoarthritis and calcific tendinopathy. Importantly, these findings could have impact on other calcifying diseases.
The research group: The project is under the supervision of Dr Sonia Nasi and Prof Nathalie Busso at the Laboratory of Rheumatology of the University Hospital of Lausanne (CHUV). The lab has 20+ years experience in microcrystalline inflammatory and degenerative arthropaties and have access and apply cutting-edge technologies. The student will be enrolled in the PhD Program in Cancer and Immunology of the University of Lausanne. Participation in this program offers unique opportunities for PhD students to benefit from high quality teaching and training from leading speakers and to collaborate with local and international experts in the field.
- Applicant should hold a master's degree in biology, medical biotechnology, biochemistry or a related discipline.
- Applicant should ideally have documented experience in cellular biology, molecular biology and in vivo mouse models. Previous experience with immunological assays, biochemical assays and bioinformatics analysis are advantageous.
- Willingness to work with animal models (mice) and human samples.
- Fluent in English.
Application: Interested students should send their application (motivation letter, CV, university diploma and detailed grades of exams, a brief synopsis of his/her master thesis, at least 2 letters of recommendation)
CHUV – Laboratoire de Pneumologie
Centre des Laboratoires – CLE D02 207
Chemin des Boveresses 155
Phone: +41 213149363
The role of microbial exposure on lung barrier development and susceptibility to allergic disease
Microbial colonization is important in the development of immune homeostasis in mucosal barrier tissues. Early life exposures including delivery mode, maternal commensals, antibiotics usage and environmental exposures can influence the composition of microbial communities. Perturbations of microbial composition can consequently alter immune development in mucosal tissues and lead to an increased susceptibility to, or exaggeration of, allergic diseases. However, studies on the effects of altered microbial composition on immune responses, barrier function and disease development have so far mainly focused on the intestine. Recent studies investigating these effects in the skin in early life have provided us with insights into the importance of microbial colonization in skin immune cell seeding and barrier development. Whether perturbations in the lung microbial composition and diversity in early life influence lung barrier function and the development of allergic lung inflammation remains to be determined.
The prevalence of atopic diseases has increased drastically over the past decades, especially in industrialized countries. Current knowledge in the field is limited to the influence of early life exposures on immune responses in the lung and susceptibility to develop allergic airway inflammation and asthma However, an important knowledge gap remains to be filled about the processes involved in the development, maintenance and function of the lung barrier in early life, and how alterations in this first line of defense against adverse environmental exposures influence the onset of disease.
This project is built on an emerging principle whereby the interaction between the microbiome, the structural barrier and immune defense is a key system for promoting and maintaining respiratory health and for protecting against lung disease. The main objective will be to identify how early life alterations in microbial exposure can affect lung barrier development and consequently influence allergic lung disease development.
CHUV – Division of Pulmonary Medicine
The research interest of the CHUV’s division of Pulmonary Medicine is to enhance our understanding of the mechanisms underlying disease initiation and progression in allergic respiratory disease with the microbiome at the center stage. In addition, we aim to identify interventional strategies for pulmonary diseases including, but not limited to, asthma, cystic fibrosis and chronic obstructive pulmonary disease,
as well as for lung transplantation, and to optimize our standard of care through translational approaches, and to optimize our standard of care through translational approaches.
The project is under the supervision of Dr. Niki Ubags and Prof. Christophe von Garnier. The laboratory has a long-standing experience in studying host-microbe interactions in allergic airway inflammation using state-of-the-art immunological and cell biological approaches and has access to clinical samples and core facilities belonging to the University of Lausanne. The student will be enrolled in the PhD Program in Cancer and Immunology of the University of Lausanne, Faculty of Biology and Medicine (https://www.unil.ch/cancer-immunology/home.html ).
Applicant should hold a master degree in immunology, biology, biomedical sciences, biochemistry or a related discipline.
Applicant should ideally have documented experience in immunology, molecular biology and both in vitro models andin vivomurine models. Previous experience with microbiology, bioinformatics analysis and immunohistochemistry are advantageous.
Willingness to work with murine models and human samples.
Fluent in English.
Applications should include: CV, motivation letter, copy of university diploma and transcripts, a brief synopsis of his/her master thesis, 3 letters of recommandation.
Prof. Caroline Arber
Department of oncology UNIL CHUV
Ludwig Institute for Cancer Research
PhD candidate position: Immuno-Oncology and T cell engineering
The laboratory “Targeted immunotherapies for hematologic malignancies” headed by Prof. Caroline Arber (https://www.unil.ch/dof/arber-barth) is recruiting a PhD student for a project developing engineered T cell therapies for acute myeloid leukemia.
You are a PhD candidate interested in the development and investigation of cutting-edge T cell engineering strategies with the goal to develop a novel approach for safe targeting of acute myeloid leukemia. You will build upon previous work performed in our laboratory that include chimeric antigen receptor (CAR) based recognition of leukemia associated antigens, combined with CRISPR based genome editing to generate an off-the shelf cellular therapy product. The project includes work with human cells from healthy donors and patients, tissue culture, flow cytometry, microscopy, molecular cloning, molecular biology, gene expression analysis and collaboration with bioinformaticians. The candidate will also assess the in vivo antitumor function of the engineered T cells in mouse models. Techniques used include in vivo bioluminescent imaging and assessment of anti-tumor response by imaging, flow cytometry and histology at specific time-points during the experiment.
The successful PhD candidate should be a highly motivated person ready to engage in this project, show good team spirit, be willing to invest energy in the setting up/ trouble shooting and optimization of novel culture systems, actively collaborate with experimentalists and bioinformaticians in the Department, and develop independent thinking to further advance and develop the project. Good oral and written communication skills in English are essential.
The Department of oncology UNIL-CHUV brings basic, pre-clinical and translational clinical research together in a spirit of innovation. It includes the services of immune-oncology, hematology, medical oncology, radiation oncology, and the Center for Experimental Therapeutics (CTE). It is also integrating the Ludwig Institute for Cancer Research (LICR) Lausanne Branch, that has an ambitious cancer research program in the field of immunotherapy. The PhD program offers a vibrant community in the fields of cancer and immunology at large, and the possibility to establish new collaborations. We are also an active member of the Swiss Cancer Center Leman.