Muscle methylation and metabolism dynamics - M3 Dynamics

The expression of a specific molecular program ruling the right process of muscle stem cells (MuSC) fate is required for regenerative myogenesis and skeletal muscle homeostasis. Muscle pathologies generally originate or result from altered MuSC fate, such as muscle wasting in aging, muscular dystrophy or rhabdomyosarcoma. Covalent post-translational protein modifications (PTMs) such as lysine methylation contribute to all aspects of cell physiology and are a primary source of protein functional diversity in mammalian cells, including muscle biology.

Our preliminary data suggest that a lysine methyltransferase participates in muscle homeostasis through epigenetic and metabolic signaling. MuSC maintenance and differentiation are controlled by gene expression programs regulated by intertwined epigenetic and metabolic mechanisms and our working hypothesis is that this methyltransferase is a key actor of MuSC fate trajectory by regulating critical epigenetic and metabolic rewiring.

To decipher its functions in muscle biology and to understand how deregulation of its signaling might alter skeletal muscle homeostasis and promote human diseases, the PhD candidate will unravel related phenotypes and biological functions of the methyltransferase in MuSC and relevant mouse model. She/he will identify the specific substrates and partners of the methyltransferase through unbiased proteomics approaches and functionally characterize the most relevant pathways at play, with a particular focus on epigenetic- and metabolic-related functions.

Altogether, we expect to identify and characterize key relevant protein methylation signaling pathways to provide better insights into muscle biology and therapeutic opportunities for related pathologies of muscle origin.

This PhD project will be co-supervised by Dr Reynoird (Institute for Advanced Biosciences, team ProMeDy) and Dr Schlattner (Laboratory of Fundamental and Applied Bioenergetics). 

IAB is an internationally renowned research center in basic and translational biomedical research hosting 19 multidisciplinary research teams and groups (300 staff)The goal shared by IAB scientists is Understanding how environment shapes biological systems – that is, the basic mechanisms by which the epigenome, cell and tissue plasticity reprogram themselves under the influence of their chemical, metabolic, physical, cellular, microbiotic and immunological environments. This approach generates both fundamental and translational advances applied to four major global challenges for human health:

Cancer prevention, early detection and experimental therapy

Genetics, epigenetics, physiology and therapies of infertility

Host-pathogen interactions, metabolism and immunity to parasitic infection

Exposome of early life exposures in relation with development and respiratory health.

The team ProMeDy research program, led by Dr Reynoird, focuses on histone-independent protein methylation signaling to explore its non-canonical epigenetic impact on chromatin function and nuclear regulations, as well as in various cytoplasmic processes. Non-histone protein methylation regulates protein function, is highly specific, and dynamically reversible—highlighting its untapped therapeutic potential. However, the full scope of protein methylation signaling remains untapped. The long-term goal of our research is to demonstrate the under-appreciated importance of lysine methylation signaling in cell homeostasis and to offer new promising clinical targets for human diseases, notably cancer.

The LBFA main interest is in regulatory circuits that maintain energetic and metabolic homeostasis, their regulation by life style factors such as nutrition or exercise, and their effects on cell death and survival. The lab aims at better understanding the molecular and cellular mechanisms that allow a cell to maintain its energy state.This depends on “high energy” compounds like ATP and phosphocreatine, in particular the ATP/ADP ratio. Different mechanisms have evolved to cope with fluctuations in energy supply and energy expenditure, as well as intracellular diffusion limitations, which constantly challenge cellular energy homeostasis.

We are looking for a highly motivated candidate with good theoretical and technical skills in molecular and cell biology.

The candidate must be enthusiastic for the project and the general field of research and is expected to have hand-on experience in at least one of the thematics of epigenetics, cell signaling and metabolism.

The candidate should hold a Master 2 or equivalent diploma by Sept. 2025.

French speaking is not required.