Thesis position – Respiratory deficits in the Congenital Central Hypoventilation Syndrome (CCHS): underlying central mechanisms and therapeutic treatments.

Congenital Central Hypoventilation Syndrome (CCHS) is a human disease caused by the mutation of Phox2b, a gene coding for a transcription factor involved in the specification of the autonome system, including groups of neurons required for proper breathing behavior. This mutation results at birth in a severe hypoventilation, which develops up to lethal apneas during sleep and a lack of central chemosensibility (no response to a high level of CO2). Human babies cannot survive unless being mechanically supported for breathing. Animal models recapitulating the most common human mutations have been developed and are currently used to investigate the central mechanisms underlying the observed respiratory deficits and more importantly to search for molecules potentially efficient in compensating central anomalies in the control of breathing. The aim of the proposed PhD program is to continue investigating central bases for respiratory deficits associated with CCHS, deciphering the role of microglia and to test one or two molecules with potential clinical relevance that could be used to alleviate the depressed respiration in mutant animals.

To achieve this goal, electrophysiological recordings of neuronal activities generated by central respiratory networks will be associated with calcium imaging on in vitro preparations and with pharmaceutical treatments to alleviate respiratory deficits on animal models for CCHS. Immunohistochemical approaches will also be performed on isolated brainstem tissue and in association with tissue transparization (Clarity method).

Knowledge in electrophysiology and neural networks would be appreciated.
• neural network
• rhythmogenesis
• mouse
• membrane properties
• breathing

Funding: FRM
Starting date: October 1st, 2025.

You want to apply?
Please send a cover letter and a CV to :
Muriel Thoby-Brisson