The project supported by my AIAS fellowship addresses fundamental scientific questions pertaining to an essential membrane transport system in humans; namely facilitated sugar transport, where new insights will have immediate scientific impact.
Facilitated sugar transport is the process by which sugar-molecules are taken up from circulation into the individual cells of the body as an ubiquitous energy and carbon-source. Furthermore sugar uptake contributes to the generation of reducing power in the cell.
Facilitated sugar transport in humans is made possible by sugar transporters called GLUTs and SWEETs located in the cellular membrane, and every cell possesses these sugar transport systems. For both GLUTs and SWEETs, structural information is sorely lacking to address important mechanistic questions to help elucidate the molecular mechanism by which they can move sugars across the cellular membrane in a efficient manner. I will address these systems using a complementary set of methods founded in macromolecular crystallography to elucidate 3-dimensional structure.
Promising preliminary results have established the feasibility of this approach. This will be followed up by characterization of the molecular mechanism in vitro and in silico, probing e.g. partner interactions, inhibitors and mutations. Parts of the characterization will be conducted in association with a well-established network of national and international collaborators.
The proposed work will help to uncover general principles of facilitated diffusion systems. Furthermore an improved understanding of sugar homeostasis in humans has tremendous potential for improving general public health, and the proposed work will stimulate pharmacological efforts to identify and develop compounds of therapeutic value for e.g. obesity, diabetes and cancer.