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Regulation of GABA Synthesis by the Mafa Transcription Factor

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Regulation of GABA Synthesis by the Mafa Transcription Factor: A Shared Mechanism in Central Breathing and Sleep Disorders

Description

Diabetic poor glycemic management is frequently associated with sleep disorders (sleep
fragmentation, nightmares, obstructive sleep apneas, fatigue) and thermoregulation defect
(sweat, hypothermia). In the central nervous system, the hypothalamic preoptic area is a
major center controlling sleep and thermoregulation, although the neuronal subtypes
controlling these vital functions are only partially characterized. Mafa transcription factor
is well known to control insulin transcription in the pancreas, but it is also expressed in
few neuronal subsets and its role(s) in the central nervous system just started to be studied.
We showed that Gad2, encoding a GABA synthesis enzyme is a direct Mafa target gene.
In that context, the goal of this experimental project is:
(1) to characterize Mafa-expressing neurons in the preoptic area and their physiological
roles in sleep and thermoregulation;
(2) to visualize the consequences of Mafa transcriptional control on preoptic GABA
synthesis using a GABA sensor and its regulation by glucose;
(3) to determine whether there is a causal relationship between Mafa regulation in the
preoptic area and diabetic sleep disorders in a diet-induced diabetic mouse model.
We will take advantage of the mouse genetic models that we previously generated and
validated in the brainstem on obstructive apneas. In the present project, we will use a cre
recombinase expressed selectively in the anterior hypothalamus to activate or inhibit Mafaexpressing neurons in the preoptic area and to delete or stabilize Mafa transcription factor
in these neurons. Altogether, this work would shed a completely new light on the molecular
mechanisms that links diabetes with some of its central comorbidities.
This original experimental project, recently granted by the Fédération pour la Recherche
sur le Cerveau (FRC, https://www.frcneurodon.org/, Paris), results from a collaboration
between Dr Laure LECOIN (Rouach team) from the Centre Interdisciplinaire de Recherche
en Biologie (CIRB) at Collège de France (Paris) and Dr Patrice Fort (SLEEP team) at
CRNL (Lyon). In January 2025, the sleep part of the project will be started in Lyon under
the supervision of PhD students by combining bidirectional chemogenetics and
polysomnography in different lines of transgenic mice generated and characterized by Dr L. LECOIN.
The dates can be slightly modified to fit in with the dates of your master’s course.

If interested and motivated, please contact ASAP: Dr Patrice FORT, DR – CNRS
Email: patrice.fort@univ-lyon1.fr
URL: https://www.crnl.fr/en/equipe/sleep
URL: https://lyonsleeplab.cnrs.fr/

Profil recherché

6 months for Master 2 in Neurosciences or Biology;
12 months for Erasmus; legal gratification, 650 euro/month

Établissement d'accueil

Centre de Recherche en Neurosciences de Lyon, in the Vinatier Campus. It’s a research center on Neurosciences with numerous thematic and domains studied.

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