Description of the thesis topic

A major factor contributing to cellular and organism aging is the accumulation of advanced glycation end products (AGEs) from proteins, lipids and nucleic acids. The glycation of these molecules mostly results from a non-enzymatic reaction with electrophilic by-products of glucose metabolism such as methylglyoxal. Several recent studies implicate glycation as an important process in the pathogenesis of Parkinson's disease (PD). The DJ-1/PARK7 gene is associated with recessive and sporadic forms of PD, and Julien Dairou's lab previously reported that DJ-1 enzymatic activity can repair glycated proteins and nucleotides. This suggests a major role for DJ-1 in protection against PD-associated glycation.
Utilizing Drosophila as an established model for studying neurodegeneration and metabolic regulation, the main goal of this PhD project is to better evaluate the role of electrophilic stress in PD pathogenesis and employ DJ-1 knockout flies to investigate in vivo the protective effects of DJ-1 against diet sugar toxicity and the accumulation of AGEs and neurotoxic glycated compounds in aging and PD conditions.
We are looking for a highly motivated candidate with a master's degree in biology and an excellent academic record. A good mastering of the English language is an advantage.

Work Context

The successful candidate will work under the co-direction of Dr Serge Birman (CNRS, ESPCI Paris – PSL) and Prof. Julien Dairou (CNRS, University Paris Cité), and he will share his research time in their respective laboratories. Research in Serge Birman's group addresses synaptic function and neurological disease models in Drosophila, focusing on pathological mechanisms of Parkinson's disease, such as the neurotoxicity of α-synuclein and environmental toxins, and the implication of oxidative stress, neuroinflammation and glycation in pathogenesis. The research interests of Julien Dairou concern metabolic and toxicological enzymology, with a special focus on xenobiotic-metabolizing enzymes and glycation repair systems, and the role of DJ-1 activity in Parkinson's disease. His group has well-recognized expertise in analytical biochemistry, particularly with targeted metabolomics approaches. Both host laboratories offer in their institute state-of-the-art technological platforms, including confocal microscopy, mass spectrometry, bioinformatics, cell culture and animal facilities.

Constraints and risks

No other specific risks that those associated with laboratory work (biological agents, chemicals). The employee will receive risk prevention training upon arrival.