Marie Gendrel
I am a newly recruited ENS associate professor in Biology at IBENS, specialized in Neuroscience
Curiosity has continually driven me. I have always been passionate in understanding how things work and naturally, chemistry, physics and biology classes became my favorite topics at school. After graduating with a degree in physics and chemistry at Paris VII University, I was still more fascinated by fundamental questions in Biology. Therefore, I continued my education in the field of Genetics and Neuroscience.
After my undergraduate degree in Biology at Paris VI University, I was selected in 2002 to join the “Magistère de Génétique” program at Paris VII University. It gave me the unique opportunity to do multiple internships at several top-level Universities and Institutes. During the second year of my master program, I was selected to attend the Pasteur neuroscience course in Paris. After attending this course, I was certain that I wanted to commit to a career in neuroscience alongside with genetics.
In 2005, I therefore decided to join the laboratory of Dr. Bessereau at the École Normale Supérieure in Paris. The laboratory is using the nematode Caenorhabditis elegans as a genetic model to study he mechanisms underlying the receptor aggregation at the neuromuscular junction. During my PhD, I identified a novel synaptic protein, LEV-9, which is essential for the clustering of ionotropic acetylcholine receptors at synapses (1). My results have revealed a novel mechanism regulating the number of receptors at the synapse relying upon extracellular protein-protein interactions.
After studying the cellular mechanisms involved in synapse formation, I decided to focus on genetic mechanisms that control the development of the nervous system and more specifically, I wanted to understand how a neuron acquires its specific subtype identity. In 2010, I joined Prof. Hobert’s laboratory at Columbia University on EMBO and HFSP fellowships. In the course of establishing fundamental regulatory mechanisms for the initiation and maintenance of GABAergic neuronal identity, I extended our knowledge on the GABAergic nervous system of C. elegans by identifying ten additional GABA-positive cell types, seven of which are neurons (4).
GABA is the main inhibitory amino-acid neurotransmitter in mature neurons. The GABAergic phenotype has been defined classically by the presence of three key players in the presynaptic neurons: (i) GAD, the enzyme needed to synthetize GABA from glutamate, (ii) VGAT, the vesicular transporter that packages GABA in synaptic vesicles, and (iii) the transporter, GAT, that recaptures GABA at the nerve terminal after its release in the synaptic cleft. During my post-doc, I have performed an in-depth revision of the GABAergic nervous system in C. elegans and I have significantly given new perspectives on what really defines a GABAergic neuron in this model organism. In particular, my work has shown that additional neurons contain GABA but do not always express GAD/unc-25, VGAT/unc-47 and GAT/snf-11. Indeed, I have identified 15 new GABA-positive neurons that do not conform to this classical definition and can be categorized into 4 different types expressing different combinations of these factors (4). Two of these types show evidence of alternative modes of GABA transport because they lack expression of known GABA transporters, VGAT/unc-47 and/or GAT/ snf-11, and they do not synthetize GABA.
Moreover, I have collaborated with two of my post-doctoral colleagues to establish a neurotransmitter atlas of the male nervous system leading to the identification of sex-shared neurons displaying sexual dimorphisms (5).
During my PhD, I was selected by the Pierre et Marie Curie University to teach cellular biology and genetics to undergraduate students. At Columbia, I have mentored two graduate students and five undergraduate students. So far, three of my undergraduate students have decided to continue their training in a PhD program. Being a teaching assistant and mentoring students are invaluable experiences that made me realize my passion and capability for teaching.
In 2017, I have been recruited as a “Maître de Conférences en Neurosciences” at the Institut de Biologie de l’Ecole Normale Supérieure (IBENS). I joined the “Inhibitory Transmission” team of Dr. Stéphane Dieudonné which allows me to combine the powerful genetic tools of C. elegans with the mouse model essential to validate human processes.
I have shown that there are alternative modes of GABA transport in C. elegans (4). Interestingly, in vertebrate dopaminergic neurons, similar observations hint towards the presence of alternative mechanisms for GABA transport too. Deciphering these new mechanisms of GABA transport will shed light into the regulation of neural circuits through inhibition. I propose to first take advantage of C. elegans, a powerful genetic model organism, to identify and characterize new presynaptic determinants of the GABAergic neurotransmission, focusing mainly on putative and known transporters. Then, I will test their vertebrate orthologues given that the already known components are very well conserved between mammals and worms. New functions for already characterized vertebrate transporters could be uncovered as it happened for the glutamate vesicular transporter 1 (VGLUT1) previously known as BNPI.
SELECTED PUBLICATIONS
1) Gendrel M, Rapti G, Richmond JE, Bessereau J-L. A secreted complement-control-related protein ensures acetylcholine receptor clustering. Nature. 2009 Oct 15;461(7266):992–6.
2) Sancar F, Touroutine D, Gao S, Oh HJ, Gendrel M, Bessereau J-L, Kim H, Zhen M, Richmond JE. The dystrophin-associated protein complex maintains muscle excitability by regulating Ca(2+)-dependent K(+) (BK) channel localization. J Biol Chem. 2011 Sep 23;286(38):33501–10.
3) Buonanno M, Garty G, Grad M, Gendrel M, Hobert O, Brenner DJ. Microbeam irradiation of C. elegans nematode in microfluidic channels. Radiat Environ Biophys. 2013 Nov;52(4):531–7.
4) Gendrel M*, Atlas EG, Hobert O*. A cellular and regulatory map of the GABAergic nervous system of C. elegans. Elife. 2016 Oct 14;5:1395. *corresponding author
5) Serrano-Saiz E1*, Pereira L1*, Gendrel M1*, Aghayeva U, Battacharya A, Howell K, Garcia LR, Hobert O*. A Neurotransmitter Atlas of the Caenorhabditis elegans Male Nervous System Reveals Sexually Dimorphic Neurotransmitter Usage. Genetics. 2017 Jul;206(3):1251–69 1co-first author *corresponding author
