Dr. Anika Böttcher
Research group 'Endocrine lineage formation'
Our primary objective at the Institute of Diabetes and Regeneration Research (IDR) at the Helmholtz Center Munich is the development of regenerative therapeutic approaches to treat diabetes mellitus - complementary and alternative to the classical immunological and metabolic therapy strategies.
Diabetes mellitus is a complex and multifactorial disease characterized by gradual loss of functional beta cell mass through beta cell dedifferentiation and/or beta cell death. Human pancreatic islet transplantation is successfully applied as a treatment but is limited to the most severe cases of type 1 diabetes (T1D) due to shortage of transplantation material from cadaveric donors. We therefore urgently need new strategies for beta cell replacement therapies. Triggering endogenous beta cell regeneration is a promising approach to restore beta cell mass and normoglycemia in diabetic patients. Beta cells are heterogeneous and differ in their glucose responsiveness, proliferative activity, maturation state, responsiveness to nutrient cues or even in the susceptibility to autoimmune attack in T1D as demonstrated by us and other labs (Bader, Migliorini et al., Nature, 2016; Tritschler et al., Molecular Metabolism, 2017). Thus, to identify and target distinct beta cell subpopulations with regenerative potential it is crucial to decipher beta cell heterogeneity in humans in more detail.
Deciphering beta cell heterogeneity in humans in health and disease
The overall goal of the project is to identify novel pathways and molecular targets to directly target specific beta cell populations to proliferate and/or mature in vivo to regenerate functional beta cell mass.
The proposed project aims i) to better understand the molecular mechanisms driving beta cell maturation and establishment and maintenance of beta cell heterogeneity, ii), to decipher and compare the molecular mechanisms underlying beta cell dysfunction and loss in type 1 and type 2 diabetes (e.g. extent of beta cell dedifferentiation in T1D and T2D) and, iii) to elucidate the impact of beta cell heterogeneity in the pathogenesis of diabetes (e.g. functional characterization of remaining beta cells in T1D).
This project will be a collaboration with the MacDonald Islet Biology laboratory at the Alberta Diabetes Institute (www.bcell.org), which will focus on the functional assessment of beta cell heterogeneity and regenerating beta cells.
The PhD candidate will work with human islet material from healthy and T1D/T2D individuals and employ cutting edge technologies such as single-cell RNAseq and bioinformatics, single-molecule RNA FISH, high-resolution imaging and CRISPR/Cas9 genome editing.
The PhD candidate will work in an international environment and stimulating atmosphere in an institute dealing with various aspects of beta cell biology including beta cell formation during embryogenesis and differentiation of beta-like cells from human stem cells.