Open Positions

The full-time or part-time internship will have an essential role in establishing a large healthspan-focused database of phenotypic and molecular traits. The student will be asked to work on a framework to collect and format a multitude of traits collected in a large genetic reference population named the Healthspan Diversity Panel (HDP). The panel was designed by scientists in our lab to decipher the genetics of healthspan in thousands of mice in a longitudinal way and includes complex data from many cardiometabolic and neurobehavioral assays. A framework to create a highly organised and ready-to-use data structure has been set up and the student will contribute to its refinement and on the establishment of tailored quality control procedures. The student will also contribute to a preliminary exploration of those unseen data and bring a fundamental contribution to all future studies that will follow in the next decade. This includes after completion of the first steps mentioned above the learning and contribution to interactive web tools to access and visualise data in creative ways.

The candidate is required to have good knowledge in programming and data management and will have the opportunity to collaborate with a multidisciplinary team composed of both wet-lab and dry-lab scientists, under the supervision and guidance of lab members.

The full-time or part-time internship student will have an essential role in supporting ongoing research projects focusing on several topics including for example Alzheimer’s disease, liver disease (such as NASH) or muscle homeostasis. The student will work on the analysis of in-house and publicly available RNA-sequencing (RNA-seq, or similar) datasets to investigate the impact of a treatment or disease condition on transcript abundance. Thanks to established bioinformatic techniques such as gene set enrichment analysis, those results can be exploited to identify the underlying affected biological pathways or, for example, associated cell types (based on single cell transcriptional signatures). The student will learn how to perform appropriate quality controls, analyze the available data according to specific research needs, obtain biological insights through interpretation, generate figures in a creative and meaningful way, and contextualize those results within the research project and the relevant literature. 

The candidate is required to have good knowledge in programming and will have the opportunity to collaborate with a multidisciplinary team composed of both wet-lab and dry-lab scientists, under supervision and guidance of lab members.

The full-time or part-time internship student will have an essential role in supporting real research projects based on the analysis of human clinical data. The Laboratory of Integrative Systems Physiology (LISP) currently has access to large databases of hundreds of thousands of participants, where genetic and clinical phenotyping data are available. In an effort to bridge mouse and human systems genetics results, a team of bioinformaticians is working on the development of computational pipelines for genetic associations or predictive analyses in humans. This includes for example genome-wide association analyses (GWAS) with both common and rare variants. This is followed by biological interpretation and characterization through analyses techniques such as functional enrichment, polygenic risk score calculation or Mendelian randomization for causal effect estimation. Those tools are used in several projects spanning from deciphering genetic components of cardiac function to identifying mechanisms of healthspan in an ageing population. For the latter, we are for example expanding our analysis framework to machine learning models for feature extraction or predictive purposes. Exploiting such genetic and phenotypic data represents by itself a remarkable challenge, given the massive size with tens of millions of data points and the large required computational infrastructures. The student will learn how to analyze the available resources according to specific research needs and how to visualize the generated results in creative and meaningful ways. The student will in particular contribute to the development of new analysis modules running on different computational platforms according to the needs.

The candidate is required to have good knowledge in programming and will have the opportunity to collaborate with a multidisciplinary team composed of both wet-lab and dry-lab scientists, under supervision and guidance of lab members.

NAFLD, non-alcoholic fatty liver disease, is estimated to affect approximately one-third of the adult population worldwide and can progress to NASH (non-alcoholic hepatitis), the leading cause of liver failure. However, until now, there is no approved drug for NAFLD/NASH.

NAFLD/NASH is typified by reduced NAD⁺ levels and impaired mitochondrial function. Our laboratory has recently discovered that α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), an enzyme of the de novo NAD⁺ synthesis selectively expressed in liver and kidneys, controls cellular NAD⁺ levels through evolutionarily conserved mechanisms. Inhibition of ACMSD boosts NAD⁺ biosynthesis and mitochondrial function in both C. elegans and murine hepatocytes. Inhibiting ACMSD pharmacologically in the mouse models of NAFLD and AKI (acute kidney injury) restored NAD⁺ levels and protected hepatic and renal functions. Humans are known to have high levels of ACMSD, which makes humans susceptible to developing NAD⁺ deficiency and hence NAFLD/NASH. Inhibiting ACMSD in human primary hepatocytes where ACMSD is highly expressed enhanced de novo NAD⁺ biosynthesis and restored impaired mitochondrial function caused by glucose-lipid treatment. Collectively, these findings highlighted the importance of ACMSD in NAD⁺ homeostasis particularly in liver and suggest ACMSD as a potential therapeutic target for the treatment of patients with NAFLD/NASH.

One of our goals is to identify potent ACMSD inhibitors and investigate their influences on NAD⁺ metabolism and mitochondrial function, with the further goal of validating their therapeutic effect on the mouse model of NAFLD/NASH. We will use cell-line-based models to screen for novel small molecule inhibitors of ACMSD that effectively increase NAD⁺ content. The compounds will be provided through a collaboration with an external partner. Candidates will be validated in mouse primary hepatocytes with fundamental mechanistic studies. Finally, depending on the results obtained from mouse primary hepatocytes, the student will be invited to assist the researchers during the behavioral phenotyping sessions and the dissection of mice fed with the candidate inhibitors.

To apply or obtain practical information please contact us.

The full-time master’s project will be a fully independent (though guided) research program within the Auwerx lab, with even application between wetlab biology techniques/practices (e.g. RNA/protein extraction, qPCR) and computational techniques (e.g. microarray analysis, metabolomic, genome-wide association studies). This project will build off of previously-established research in the Auwerx laboratory, with a particular focus on systems genetics approaches to understand metabolic homeostasis, common metabolic diseases (type 2 diabetes, obesity, atherosclerosis) and aging. A profound interest and expertise in one of these areas are hence a must. Given that computational approaches are an important aspect of this project, the candidate should also have a strong background and interest in one or more of the following areas: computational biology, mathematics, statistics, or genetics.The overarching project goal will be defined, but the specifics of the final project are entirely up to the student after an introductory period. The general plan is for a mixture of bioinformatics/statistics and benchwork, but the exact breakdown will be defined mutually between the student and laboratory leadership.

The full-time master’s project will be the characterization of a novel mitochondrial stressor in the Auwerx Lab. Mitochondria are principal regulators of cellular function and metabolism. Dysfunctional mitochondria have been associated with a variety of disorders and aging. To cope with diverse changes, mitochondria have evolved the mitochondrial stress response (MSR) network to reconstitute cellular homeostasis by preventing mitochondrial proteotoxicity (mitochondrial unfolded protein response, UPR^mt) and by redistributing (mitochondria dynamics) and removing irreversibly damaged elements of the mitochondria (mitophagy). Activating MSR pathways have shown beneficial effects in aging and aging-related disorders. This project will focus on the characterization of a novel MSR inducer in mammalian cells, which includes the following work:

1. Culture mammalian cell lines
2. Isolate RNA, genomic DNA for qRT-PCR
3. Isolate protein for Western blot
4. Isolate mitochondria for BN-Page
5. Mitochondrial assays including cell respiration, ATP production, NAD consumption, ROS generation, mitochondrial membrane potential and morphology analysis, and so on.
6. Virus packaging and gene editing

The student will work under the guidance of a post-doctoral fellow in the lab.

Ceramides in Protein Aggregate Myopathies

Protein aggregate myopathies (PAM) are a group of inherited or acquired neuromuscular disorders characterized by aggregation of protein within the muscle fiber. The biochemical events that underpin the pathological protein aggregation and progressive muscle deterioration in PAM are poorly understood. Recent findings from our laboratory studies have indicated that inhibiting thede novo synthesis of ceramides, the major scaffold for most complex sphingolipids, to restore their homeostatic levels can exert therapeutic effects on muscle deterioration through protein homeostasis (proteostasis) remodeling. (Laurila et al., STM, 2022; Lima et al., under revision). These emerging insights on the cellular functions of sphingolipids provided us with a new avenue of research that has broader significance to PAM and related proteinopathies.

The proposed project will aim to validate the ceramide de novo pathway as a therapeutic target for PAM using both in vitro and in vivo approaches with mouse models and muscle-specific gene therapy.

The student will perform cell culture of different kind of muscle cells (immortalized, human, primary) and test different new chemical entities and use genetic approaches to knockdown target gene (CRISPR, Adenovirus-mediated gene silencing). Toxicity (by different luminescent assays), protein aggregation (by immunofluorescence and confocal microscopy), proteostasis (by western blot) and other in vitro relevant assays will be performed by the student.

The student will also work on mouse tissues (muscle mainly) to study the efficacy of the new chemical entities, with immunofluorescence, immunochemistery, qPCR and western blot.

The student will work under the guidance of a post-doctoral fellow in the lab.

Drug development for non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide, affecting 25% of the adult population. NAFLD is a condition caused by a build-up of fat in the liver; its development is closely connected to obesity, type 2 diabetes, impaired lipid metabolism and insulin resistance, conditions that have also risen over the past decades. In our laboratory, we are testing innovative treatments against inflammation and fibrosis in NAFLD, using a combination of in vitro and in vivo models, including a model of dietary NAFLD achieved by feeding mice a high fat/high sucrose diet. The aim of the project is to evaluate the efficacy of candidate compounds, as well as characterizing their mechanism of action.

The student will perform cell culture using mouse and human hepatocyte cell lines and/or primary hepatocytes, in order to evaluate the effect of compounds on cell viability, mitochondrial function and lipid overload using specific in vitro assays. The student will also support the in vivo study, helping researchers with mouse phenotyping and working on the analysis of mouse tissues by qPCR and western blot.

Graduate or post-doctoral project in the Auwerx laboratory on the “Multilayered analysis of the mouse genetic reference populations” involving a mixture of wet and in silico approaches in systems biology and genetics.

This project will build off of previously-established research on the BXD mouse genetic reference population in the Auwerx laboratory within the overall spectrum of metabolism. The primary project will focus on computational techniques (informatic/mathematical/statistical/genetic/omics) as applied on massive and multilayered datasets (genomics, transcriptomics, proteomics, metabolomics, phenomics) previously generated by the lab in the BXD mouse population. The student/post-doctoral fellow will be able to work on a range of projects which have strong leads in the directions of glucose homeostasis and metabolism, exercise physiology, neurodegeneration, and aging. The mouse data will be integrated with comparable large datasets collected in similar population studies in the Drosophila Genetic Reference Panel (DGRP) and in human GWAS. Although the student/post-doctoral fellow will be extensively exposed to wetlab biology techniques, a large part of the work will involve data analysis. The candidate should hence not only have a strong background and interest in metabolism, but also excellent in one or more of the following areas: mathematics, statistics, or genetics.

To apply or obtain practical information please contact us.