I am a PhD student in the group of Dimitrios Fotiadis at the University of Bern. In our laboratory, functional and structural studies of transporter proteins are performed. Transporters are fascinating because they are involved in numerous key cellular processes and their dysfunction can lead to serious diseases. Furthermore, the number of available structures of transporters and membrane proteins in general is relatively low compared to soluble proteins. In my TransCure project, I am focusing on the overexpression of human amino acid transporters for subsequent crystallisation and structure determination by x-ray crystallography. Structure determination of human transporters is important in understanding their molecular working mechanisms and for structure-based drug design.
I have been a postdoctoral fellow in Kaspar Locher’s laboratory at ETH Zurich since December 2013. The main goal of my research is to understand the structural basis of substrate recognition and transport by human ABCG2, as well as its specific inhibition by small molecules and protein binders (such as antibodies and nanobodies). ABCG2 is a multidrug ABC transporter that limits the oral bioavailability of drugs and extrudes anti-tumour compounds in cancer cells, thus contributing to multidrug resistance. In our lab, we are using cryo-EM to study nanodisc-reconstituted ABCG2 in distinct conformations, both in-house and in collaboration with Henning Stahlberg (C-CINA Basel). We have developed robust functional assays in proteoliposomes, nanodiscs and detergents, which complement and guide our structural findings and interpretations. Finally, in collaboration with Karl-Heinz Altmann (ETH Zurich), we are probing synthetic small molecule inhibitors, currently based on Ko143, to further contribute to our understanding of ABCG2 function and inhibition, and to provide a basis for the design of novel inhibitors and modulators in the future.
In October 2016, I joined the group of Karl-Heinz Altmann at ETH Zurich as a PhD student, after graduating with an MSc in Pharmaceutical Sciences from the University of Basel. My project is focused on the development of novel ligands for human L-type amino acid transporter 1 (LAT1/SLC7A5). Overexpression in different types of human cancers suggests that inhibitors of LAT1 may be potential antitumour agents. Recently, we have been able to deliver the first nanomolar LAT1 inhibitor discovered within the TransCure network. In addition to the various benefits arising from the multidisciplinary nature of the network, the NCCR TransCure offers a wide range of further education courses. One such specialised course at Novartis Basel allowed me to gain valuable insights into industrial drug discovery and development.
Martin Weisstanner (Alumni)
In 2010, at the very beginning of the NCCR TransCure, Matthias Hediger gave me the opportunity to switch from bench to ‘deskside’ by offering me the job of Scientific Officer. My tasks were still closely linked to science but from another point of view. My duties included the coordination of the annual reporting to the SNSF, support of the management of ongoing research projects, and the organisation of international scientific conferences (BioMedical Transporters). Since 2015, I have applied the management skills learned at the TransCure in an environment that is much further away from science, as a member of the Staff of the Executive Board of the University of Bern. In this function, I support the Executive Board in (financial) strategic planning and organise the yearly strategic meetings with the faculties and centers of excellence.