Kamran Ahmed L&S Sciences
Investigating how mTORC1 Hyperactivity Affects Autophagy and Mitophagy in Dopamine Neurons
The mammalian target of rapamycin complex 1 (mTORC1) is a protein complex that activates protein synthesis, modulates cell growth and proliferation, and regulates autophagy. Loss-of-function mutations in the TSC1 or TSC2 genes, which negatively regulate mTORC1, result in complex hyperactivity causing the syndromic neurodevelopmental disorder Tuberous Sclerosis Complex (TSC). TSC patients have a wide variety of clinical presentations including high comorbidity rates with neuropsychiatric disorders in which the dopaminergic system has been implicated. Little is known about the impact of mTORC1 disruption on the dopaminergic system. Previous work showed that normal autophagy and mitophagy processes in cortical neuronal cultures are disrupted by mTORC1 hyperactivation. My project will explore how Tsc1 gene deletion in mouse dopamine neurons affects autophagy and mitochondrial function of this cell population. We consistently observe that Tsc1 knock-out dopamine neurons are very large in size, leading to the hypothesis that in addition to protein overproduction, these cells may further fail to degrade old proteins and organelles. Characterizing how autophagy and mitochondrial function are impacted in dopamine neurons will be necessary to understanding cellular and resulting behavioral dysfunction brought about by mTORC1 hyperactivation.
Message To Sponsor
Thank you for sponsoring such an incredible experience. I know my peers and I have become better scientists in the process. Personally speaking, this program has reinforced my pursuit for a neurobiology PhD. Moreover, the collaborations, cluster meetings, and conference presentations have augmented my passion for research.