Alzheimer’s disease (AD) is the most widespread neurodegenerative pathology in the world, representing an economic, societal and scientific challenges. The failure of current treatments is associated with the multifactorial nature of this disease, involving not only a proteopathy and a deficit in synaptic plasticity impacting cognitive functions, but also a dysfunction of mitochondrial homeostasis. Alterations of mitochondria structure and function occurs in early-stage AD brains likely contributing to disease development. Moreover, the specific process removing damaged mitochondria (mitophagy) is compromised in both sporadic and familial forms of AD and occurs in the brain and in peripheral cells, resulting in the accumulation of dysfunctional mitochondria. However, the mechanistic insights and the cellular landscape of mitophagy failure in AD are unknown. An exploratory analysis using the ​“Nanostring” approach has identified a deregulation of a set of genes whose role in regulating mitochondrial dysfunction and mitophagy have not been studied yet in AD. The project aims to elucidate original molecular mechanisms leading to the alterations of mitochondria structure and function and the failure of the degradation process of dysfunctional mitochondria. 

They will characterize regulations occurring at the transcriptional, translational and post-translational levels of novel signaling cascade implicating new genes likely related to mitochondria dysfunction and mitophagy failure in AD. They will study mitochondria dysfunctions and mitophagy process in a brain cell-type and spatio-temporal specific manner. This project will be developed using complementary AD study models including human-derived brain samples, induced-pluripotent stem cells (iPSC) and murine study models mimicking AD (humanized knock-in AD mouse model). This is a multidisciplinary project involving neurobiology, mitochondrial biology, synaptic plasticity and neuroimmunology. The obtained results will contribute to advance our knowledge for AD pathogenesis, allowing the development of new therapeutic approach to prevent or revers AD pathology.

Dr. Mounia Chami
https://​cvscience​.aviesan​.fr/c…

Co-PI: Dr. Kasturi Mitra
https://​www​.ashoka​.edu​.in/prof…

Candidates should have at least one first author publication in a relevant journal. Candidates with cell and molecular biology background with interest in neuroscience will be preferred. Expertise in handling primary neurons cultures, Confocal microscopy, animal experimentation would be a plus.

Candidates interested in applying for 2 competitive French fellowships should email their detailed CV and cover letter to mchami@​ipmc.​cnrs.​fr and Kasturi.​mitra@​ashoka.​edu by March 22^nd, 2024. The chosen candidate(s) will write the fellowship in consultation with the PI and Co-PI and submit the application timely. If funded, the collaborative study would be carried out in the affiliated locations of the PI and co-PI based on project requirement.