Bioactive targets of mitochondrial quality control and function
Gradual decline of mitochondrial quality is a hallmark of aging and the cause of age-related chronic diseases such as diabetes, cancer and neurodegeneration. Removal of dysfunctional mitochondria through targeted autophagy (a process known as mitophagy) and parallel replacement with functional mitochondria via biogenesis is a critical step in maintaining cellular homeostasis and a natural deterrent against age dependent dysfunctions.
Bioactive compounds that stimulate healthy mitochondrial turnover are therefore thought to be beneficial for a broad range of common diseases and object of major interest. A current obstacle in identifying such compounds is the heterogeneity of mitochondria in different tissues as well as the fact that derived cells quickly loose cell-specific characteristics due to artificial, glycolysis-favouring, in vitro conditions of culturing. Furthermore, imaging of mitochondria in living rodents is challenging and in vivo screening of products targeting mitochondrial function is not practical.
To circumvent this problem we aim therefore to develop “biosensor” zebrafish lines to visualize molecular processes regulating mitochondrial quality control in vivo and use these tools to identify bioactive molecules that trigger mitochondrial quality check and control via mitophagy as well as ultimately replacement by biogenesis. To this end, we take advantage of the dynamic induction of the translocator protein 18kDa (TSPO), which resides in the mitochondrial outer membrane and accumulates at high levels in cells that are exposed to metabolic, oxidative or inflammatory stress.
ELIGIBILITY AND APPLICATION
This four-year studentship is funded jointly by the BBSRC London Interdisciplinary PhD Programme and Nestle’ Institute of Health Sciences. It covers UK/EU tuition fees and an annual tax-free stipend in the region of £16,057 (exact amount confirmed each year).
Applications will be considered from candidates who hold/or expect to gain a first or upper second class honours degree (or equivalent) an MSci or Masters degree from a range of disciplines such as medicine, veterinary medicine, biological sciences, animal sciences, social sciences, statistics and economics. Candidates with a lower second-class degree supplemented by a Masters qualification (in a relevant subject) will also be considered.
For more information regarding the project, please contact Dr Michelangelo Campanella - firstname.lastname@example.org
For more information about the programme, eligibility or the application process please contact the programme administrator - email@example.com
UK/EU tuition fees and an annual tax-free stipend in the region of £16,057 (exact amount confirmed each year).