Pancreatic islet development and beta cell mass
Metabolism and Cell Signaling
Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM (IIBM)
DESCRIPTION OF THE OFFER
Beta cell mass is an important component of type 2 diabetes progression, lower beta cell mass is associated with reduced insulinaemia, glucose intolerance and diabetes. Beta cell mass is highly heterogeneous among human individuals, and currently there are no methods for its clinical determination. Genetic information that predicts this, could become a cost-effective tool for diabetes diagnosis, treatment and prevention strategies; a great potential clinical asset in that could allow stratification of diabetes patients in the era of personalized medicine.
The objectives of the group are to determine the genetic basis of beta cell mass, focusing in pancreas development, but also in processes that allow compensatory mechanisms in pathophysiological conditions (pregnancy, obesity, aging). To achieve this goal, we study type 2 diabetes genetic risk loci, and characterize the molecular mechanisms of their association to disease. We study this using two “state-of-the-art” techniques, which the students will be able to master upon competition of the project.
- Gene editing by CRISPR techniques, which allows gene loss-of-function studies, and evaluate the effects of single-nucleotide polymorphisms.
- Differentiation of pluripotent stem cells: allowing the “in vitro simulation” of human pancreas development. This way we can study the effects of genetic perturbations on pancreatic progenitors.
We know that adult beta cell mass is determined by the size and proliferation of the pancreas progenitor pool. Quantifying such proliferation, and the effect of genetic variants on this, is the best approach to survey an event that can explain the high heterogeneity in cell mass observed in adults, but this was out of reach until recently. The long-term objective of these studies is to translate the findings into the clinic. Linking genetic information to physiopathological events will allow personalized diagnostic and treatment of type 2 diabetes,