Laureates of the ANR PRCI call 2024

Congratulations to the 2025 winners of the ANR call for projects for collaborative research – international (PRCI), Daniel Choquet (IINS), coordinator of a Franco-German project and François Ichas (IMN), coordinator of a Franco-Swiss project.

Projects

RECODE
Understanding synaptic complexity through the recoding of endogenous neuronal receptor complexes using genetic code expansion and genome editing

ANR/DFG PRCI 2024 “Franco-German”

Involved Laboratories:

• Daniel Choquet, French coordinator (IINS, CNRS Bordeaux Neurocampus, France)
• Markus Sauer/Gerti Beliu, German coordinators (Center for Biotechnology and Biophysics, Würzburg, Germany)

Project Summary and Impact
The RECODE project focuses on unraveling synaptic complexity using cutting-edge techniques such as genetic code expansion and genome editing. Specifically, it aims to study the diversity of AMPA receptor complexes, which are critical for rapid synaptic transmission and plasticity, through innovative bioorthogonal labeling and super-resolution imaging methods. Labeling the various components of receptor complexes remains particularly challenging with conventional techniques. Combining molecular biology and neuroimaging approaches, our work will enable nanoscale mapping of the dynamics and subcellular localization of these receptors in their native environment. By bringing together two teams of excellence, this project promises groundbreaking advances in determining the organizational dynamics of synaptic complexes, providing critical insights into the neuronal mechanisms underlying learning and memory.

Quality and Relevance of the Partnership
The partnership between Daniel Choquet’s team (France) and Markus Sauer/Gerti Beliu’s team (Germany) is built on exceptional complementarity and internationally recognized expertise. Choquet’s lab excels in studying the biology of synaptic receptors and neuronal mechanisms, while Sauer/Beliu’s team leads in the development and application of super-resolution imaging techniques and genetic code expansion labeling. This synergy enables the combination of innovative molecular approaches, including genome editing, with nanoscale imaging tools to study synaptic dynamics with unprecedented precision. Their previous successful collaboration highlights their ability to overcome technical challenges and achieve significant scientific breakthroughs. This Franco-German partnership, grounded in a shared vision and clear objectives, ensures an integrated, multidisciplinary approach to addressing fundamental questions about synaptic plasticity and function.

 

étioMSA
Understanding Multiple System Atrophy pathogenesis at the molecular and cellular level

ANR/SNF PRCI 2024 « Franco-Swiss »

Involved labs:

• François Ichas, Coordinator France, (CNRS Bordeaux Neurocampus, France, website)
• Henning Stahlberg, Coordinator Switzerland, (EPFL, Lausanne, Switzerland, website)

Scientific Relevance:

Multiple System Atrophy (MSA) is one of the most devastating neurodegenerative diseases. It is also one of the fastest, leaving patients with only a few years of remaining life expectancy after diagnosis. We have identified an alpha-synuclein fibril strain that, when seeded into mouse brains, reproduces the same disease pattern as observed in human MSA patients. This parallelism includes molecular ultrastructures, cellular distribution and propagation, prion-like spreading behavior, and overall disease symptoms.

We will leverage this parallelism to study the mechanisms underlying MSA in detail using this model. Our findings will likely provide unprecedented molecular insight into the mechanisms responsible for fibril pathology, fibril spreading, and damage to cellular functions. Such discoveries may also be applicable to other, slower-progressing synucleinopathies, such as Parkinson’s Disease and Dementia with Lewy Bodies.

Impact:

Neurodegeneration encompasses a group of human brain diseases, including Alzheimer’s and Parkinson’s Disease, where—despite massive investments and decades of effort by academia and industry—we remain largely powerless against these devastating and often deeply saddening conditions.

If our proposed research succeeds in providing a molecular understanding of the disease mechanism in Multiple System Atrophy (MSA), this knowledge is likely to enhance our understanding of other, similar diseases, such as Parkinson’s Disease, Dementia with Lewy Bodies, and even Alzheimer’s Disease. For the first time, this would offer molecular insight into the mechanisms underlying fibril seeding, spreading, and selective cellular damage. Such knowledge could significantly advance our fight to prevent this large class of neurodegenerative diseases.