© copyright Loic Salmon 2016

Loïc SalmonCentre de résonance magnétique nucléaire à très hauts champs de Lyon (CRMN) - CNRS / Université Claude Bernard / ENS Lyon

ATIP-Avenir
Connecting RNA fundamental biophysics to biological function by understanding RNA conformational dynamics

Mes recherches

I am a Nuclear Magnetic Resonance (NMR) spectroscopist that investigate complex biological molecular processes at atomic resolution. I am therefore constantly working at the crossing of physics, chemistry and biology, with a continual interplay between theory and experiments. During my Ph.D. thesis (2007-2010) in Grenoble at the Institut de Biologie Structurale with Martin Blackledge I discovered how NMR spectroscopy can be used to study conformational dynamics in folded and unfolded proteins. To understand fondamental properties of nucleic acids, I then moved in 2011 to Ann Arbor at the University of Michigan to work with Hashim Al-Hashimi. I subsequently joined the lab of James Bardwell in 2014 to decipher the transient but essential interaction between chaperone proteins and their substrates. In 2016 I moved to ETH Zurich as a Marie Sklodowska-Curie Fellow to investigate the mechanism by which DNA synthesis can be initiated. End of 2017 I arrived in Lyon at the Very High Field NMR Center as a CNRS researcher where I currently lead a team focusing on complex dynamic in RNA molecules.

Mon projet ATIP-Avenir

Investigating micro-RNA Dynamics using Paramagnetic NMR Spectroscopy

PARAMIR

Recent decades have revealed an ever-increasing diversity of RNA functions. These discoveries have profoundly modified the conceptual framework of molecular biology. RNA functional diversity is often triggered by conformational changes. Therefore describing these dynamics at atomic level is key in understanding the functioning of RNA, refining our fundamental biochemical and biophysical conception of RNA and opening new avenue for bioengineering or rational RNA oriented drug discovery.

Micro-RNAs are a fascinating class of small non-coding RNA that play essential roles in RNA induced gene silencing and are estimated to target in humans up to 60% of protein coding genes. Despite their crucial biological importance, the conformational behavior of micro-RNAs remains quite elusive.

NMR spectroscopy is extremely well suited to investigate this question, however accessing an accurate description of RNA conformational dynamics has remained a considerable challenge. The sparsity of measurable data is the limiting factor in RNA dynamic studies by NMR. I am proposing to bypass this obstacle by developing paramagnetic NMR for RNA and the adequate computational and analytical tools to decode this rich experimental information. This will provide a general tool to investigate RNA structure and dynamics at an unprecedented resolution.

Loïc Salmon est également lauréat ERC Starting Grant 2018 et a bénéficié du label ATIP-Avenir.