Marie Curie (MSCA) doctoral network NADIS - PhD studentship (EPFL - ESR10)

We look for a doctoral candidate/ESR in the NADIS project “NAD+ International Scientist-Training” to explore NAD+ metabolism and its biological effects, with a focus on adipose tissue progenitor and stem cells in different life stages and physiological situations. The research will be developed at one of the two Swiss Federal Institutes of Technology, the Ecole Polytechnique Fédérale de Lausanne (EPFL) and will include secondments in other laboratories from the NADIS network.

What will you do?

ESR10: Understanding the uniqueness and physiological impact of different NAD+ metabolic routes

Hosts: Dr. Carles Canto and Prof. Bart Deplancke

Duration: 48 months

Project description: Decreases in intracellular NAD+ levels have been proposed as a hallmark of metabolic diseases and age-related physiological decline. This is related to the fact that NAD+ is an essential molecule for life, participating in multiple metabolic reactions as a redox cofactor and as a substrate for different families of enzymes linked to cellular metabolism, transcriptional regulation, genomic stability and DNA damage repair, amongst others. Adipose tissue is a critical organ in the regulation of whole body metabolism and its dysregulation leads to a large array of health complications, including endocrine disorders, ectopic lipid deposition, chronic inflammation and altered response to insulin. In normal circumstances, the physiological role of adipose tissue is to maintain whole body energy balance by regulating energy storage and utilization according to systemic energy demands, while simultaneously protecting peripheral tissues from lipid overloading and lipotoxicity. This is achieved through a delicate balance of positive and negative signals regulating adipocyte stem cell differentiation and the expansion capacity of mature adipocytes. We hypothesize that NAD+ metabolism will play a role in determining these processes.

The specific objectives of ESR10 will be to identify the underlying mechanisms regulating the function and communication of different cells types in the adipose stem cell niche. The project will evaluate how NAD+ metabolism participates in these processes and whether altering NAD+ levels can be used to modify the composition and adipogenic capacity of adipose stem cells in subcutaneous and visceral adipose tissue. We will also use a variety of experimental settings in mice to evaluate how different physiological challenges and disease situations alter the adipose tissue stem cell niche composition and function, as well as NAD+ metabolism.

Your main tasks and responsibilities in this project are:

- To isolate, culture and differentiate different adipose stem cell lineages from tissue biopsies, including different fat depots from mouse interventions.

- To perfom genomic and transcriptomic analyses in the adipose stell cell niche of mice exposed to different physiological challenges, which will help discerning differences in the expression of NAD+ metabolic enzymes.

- To evaluate how different NAD+ precursor molecules (vitamin B3s) alter the proliferation and adipogenic potential of different adipose progenitor cells.

The NADIS project

The main goal of the NADIS consortium is to train the next generation of metabolic researchers, providing them with in-depth knowledge and cross-disciplinary expertise to combat disease. The research projects will specifically focus on the metabolism of NAD+, a central redox cofactor and enzymatic substrate that plays an essential role in virtually all major cellular functions. The limited knowledge on the interplay between NAD+ and the cellular processes in which it is involved, especially those that lead to disease, requires novel experimental and analytical tools combined with a strong interaction between scientists and clinical staff coming from different disciplines. We aim to fill these gaps by training ten highly-skilled ESRs. To do this, we bring together our expertise in molecular and cellular biology, bioinformatics and Artificial Intelligence (AI), omics, drug development and nutritional/clinical applications. Our non-academic beneficiaries are focused on the development of nutrition products, medical foods and drug development for new therapies. We will also provide ESRs with transferable and networking skills, and first-hand experience of industrial applications, enabling them to become future leading scientists at the forefront of metabolic research and, specifically, NAD+ research in Europe.

The Ecole Polytechnique Fédérale de Lausanne (EPFL)

The Ecole Polytechnique de Lausanne (EPFL) is a public research university located in Lausanne, Switzerland. It specializes in natural sciences and engineering. It is one of the two Swiss Federal Institutes of Technology, with three main missions: education, research and innovation. EPFL counts with different. EPFL is organised into eight schools, among which the school of life sciences (SV). The School of Life Sciences counts with 52 research laboratories, grouped into four institutes, with strong inter-institute connections providing and interdisciplinary environment stimulating innovative research. SV EPFL offers Bachelor and Master programs in Life Sciences Engineering, as well as four Doctoral programs in biotechnology and bioengineering, computational and quantitative biology, molecular life sciences and neurosciences. EPFL professors have diverse backgrounds – biology, chemistry, physics, engineering, computer science, psychology and medicine – and bring together their specific perspective to tackle fundamental questions in biological sciences and solve biomedical problems to increase human knowledge and address key societal issues.

The Laboratory of Systems Biology and Genetics (LSBG)

The project will be developed at the Laboratory of Systems Biology and Genetics (LSBG) headed by Prof. Bart Deplancke, at the Institute of Bioengineering of the Ecole Polytechnique Fédérale de Lausanne, under the supervision of Prof. Bart Deplancke and Carles Canto. The central research focus of the LSBG is to understand genome organization, regulation, and variation, which is done in a multidisciplanary environment with topics ranging from microfluidics to cell biology. The lab is composed by 20-25 international researchers, including post-docs, PhD candidates and master trainees. The lab is fully equipped for biochemistry, molecular biology and cell biology studies. Most notably this includes state-of-the-art single cell and single nuclei RNA-seq capacity. The lab is part of the school of life sciences (SV) at EPFL, which has multiple platforms, including flow cytometry, mass-spectrometry, life imaging, animal experimentation and histology.