Changing the World
Are you up for a challenge and not necessarily concerned with instant gratification? Are you a pioneer at heart who is willing to ‘’take the road less traveled’’ and systematically tackle difficult research questions but with the eventual promise of great reward? If you have answered ‘’yes’’ to these rhetorical questions then this study is the perfect match to satisfy your innate curiosity and determination!
What is it about?
For this preclinical study, we are focusing on the damaging role of high sugar levels (hyperglycemia) and its impact on the development of insulin resistance/diabetes and heart diseases. Here previous data generated by our laboratory demonstrated that excess glucose availability can increase flux through several non-oxidative glucose pathways that in turn trigger the development of insulin resistance and heart diseases. However, there is a ray of hope as we propose that the activation of the pentose phosphate pathway can limit such detrimental effects. We are specifically focusing on the role of Transketolase-like Protein 1 (TKTL1), a key enzyme of the pentose phosphate pathway as very little is known about its function (in general) and under hyperglycemic conditions. The CMRG is – as far as we know – one of a handful of laboratories worldwide trying to decipher what this enzyme actually does, and our early data suggest that it offers therapeutic promise.
TKTL1 knock-out mouse breeding and analyses, ex vivo heart functional analyses, in vivo heart functional analyses, vascular functional assessments, proteomics, real-time quantitative PCR, Western blotting, ELISAs, metabolic pathway analysis, oxidative stress tests, cell culture experiments to overexpress/inhibit TKTL1 and determine downstream effects.
Prof. Johannes Coy, Tavargenix GmbH, Frankfurt, Germany
Prof. Ismail Laher, University of British Columbia, Canada