Lars Sørensen: Studies on the membrane interaction of activated coagulation factor V

PhD defence, Tuesday 13 November 2018. Lars Sørensen.

2018.11.13 | Lisbeth Heilesen

Lars Sørensen

Activated coagulation factor V (FVa) is an important regulator of the blood clotting cascade. FVa facilitates the generation of thrombin. This action requires the presence of a negatively charged membrane. Here I will present my results on using the nanodisc membrane mimic system, developed in the Sligar laboratories, for structural studies of membrane bound FVa. In addition to this, I will present the use of the nanodisc as a membrane mimic in functional studies. Furthermore, I will present the results on using the nanodisc for determining the kinetic and affinity membrane binding parameters of FVa with surface plasmon resonance and microscale thermophoresis. Here I will also include the results on studying the structure of membrane bound FVa with negative stain electron microscopy and why liposomes were used for characterizing the conformational changes of FVa upon membrane binding to a liposome. The results of using hydrogen deuterium exchange measured by mass spectrometry to characterize the conformational changes of FVa bound to a liposome will also be presented.

The PhD degree was completed in the interaction characterisation department at Novo Nordisk and the Section for Structural Biology at the Department of Molecular Biology and Genetics, Science and Technology, Aarhus University.

This résumé was prepared by the PhD student.

Time: Tuesday, 13 November 2018 at 13:15
Place: Building 3130, Conference room 303, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus C
Title of PhD thesis: Characterization of the activated coagulation factor Va membrane interaction with HDX-MS and towards structural studies of the activated coagulation factor Va inactivation complex
Contact information: Lars Sørensen, e-mail: lssx@novonordisk.com, tel.: +45 20252848
Members of the assessment committee:

Professor Michael Lund Nielsen, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Denmark
Professor Thomas Günther-Pomorski, Department of Biochemistry II – Molecular Biochemistry, Ruhr University Bochum, Germany
Professor Finn Skou Pedersen (chair), iNANO and Department of Molecular Biology and Genetics, Aarhus University
Main supervisor:
Academic: Professor Poul Nissen, Department of Molecular Biology and Genetics, Aarhus University
Industrial: Head of Department Johan Faber, Novo Nordisk
Co-supervisor:
Academic:
Thomas Boesen, Department of Molecular Biology and Genetics, Aarhus University
Professor Steven G. Sligar, Department of Biochemistry, University of Illinois Urbana-Champaign
Professor Jim Morrissey, Department of Biological Chemistry, University of Michigan
Industrial:
Principal Data Science Programmer Kristoffer W. Balling, Novo Nordisk
Research Scientist Lisbeth Moreau Andersen, Novo Nordisk
Language: The PhD dissertation will be defended in English

The defence is public.
The PhD thesis is available for reading at the Graduate School of Science and Technology/GSST, Ny Munkegade 120, building 1520, rooms 128-134, 8000 Aarhus C.

PhD defense