PROJECT
SUPERVISORS
Project Supervisor
Mathias Ziegler
Background
I received medical training combined with profound education in natural sciences at the Medical University Moscow. Biomedicine was a very new discipline at the time intending to generate scientists at the interface between fundamental research and clinical practice. Inspired by the opportunity to get insights into basic molecular mechanisms underlying clinical manifestations of diseases, I continued with a Ph.D. in biochemistry at the Charité Berlin focusing on mitochondrial nucleotide metabolism. During my 3-year postdoc at SUNY Syracuse, USA, I had the privilege to work with a pioneer in the discovery of the mechanism of mitochondrial ATP synthesis.
Back in Berlin, at the Free University, I started my own group and an exciting journey into the discovery of NAD as a signaling molecule. 20 years ago I moved to Bergen, Norway, where I am now a professor at the Department of (sic!) Biomedicine. Currently, we are excited about the regulation of PARPs, sirtuins and NADases by fluctuations in subcellular NAD pools, especially the mitochondrial one. Recently, we have initiated a program investigating the metabolic and functional interplay of B vitamin-derived cofactors (NAD, CoA, FAD…).
Research
Most biological processes require energy and are tightly regulated. Energy is extracted from food supplies and eventually transformed into ATP. These pathways consist of many reactions which involve NAD or NADP, small molecules which serve as intermediate energy transmitters. Vitamin B3 is essential for the synthesis of these nucleotides. Interestingly, the key molecules in energy transduction also have important roles in the regulation of all vital cellular activities.
NAD-dependent signaling processes are mediated by PARPs, Sirtuins or NAD glycohydrolases by posttranslational modifications or the generation of messenger molecules. Our current work is aimed at further dissecting the molecular mechanisms of this network connecting cellular energy and signaling transmission. We are particularly fascinated by the dual roles not only of NAD, but also other cofactors such CoA, FAD or S-adenosyl methionine and the interaction of these molecules in metabolism and signaling.
Publications
Houry D, Raasakka A, Ferrario E, Niere M, Bifulco E, Kursula P, Ziegler M. (2023) Identification of structural determinants of nicotinamide phosphoribosyl transferase (NAMPT) activity and substrate selectivity. J Struct Biol. 215(3):108004. doi: 10.1016/j.jsb.2023.108004
Strømland, Ø., Kallio, J.P. … Brakhage, A.A. and Ziegler, M. (2021) Discovery of fungal surface NADases predominantly present in pathogenic species. Nat Communic https://doi.org/10.1038/s41467-021-21307-z
Luongo, T.S., Eller, J.M., Lu, M.-J., Niere, M., Raith, F., Perry, C, Bornstein, M.R., Oliphint, P, Wang, L., McReynolds, M.R., Migaud, M.E., Rabinowitz, J.D., Johnson, F.B., Johnsson, K., Ziegler, M., Cambronne, X.A., and Baur, J.A. (2020) SLC25A51 is a mammalian mitochondrial NAD+ transporter. Nature, https://doi.org/10.1038/s41586-020-2741-7
Bockwoldt, M., Houry, D., Niere, M., Gossmann, T.I., Reinartz, I. Schug., A., Ziegler, M., Heiland, I. (2019) Identification of evolutionary and kinetic drivers of NAD-dependent signaling. Proc Natl Acad Sci USA 116, 15957-15966, 10.1073/pnas.1902346116
Love, N. R., Pollak, N., Dölle, C., Niere, M., Chen, Y. Y., Oliveri, P., Amaya, E., Patel, S., and Ziegler, M. (2015) NAD kinase controls animal NADP biosynthesis and is modulated via evolutionarily divergent calmodulin-dependent mechanisms. Proc Natl Acad Sci USA 112, 1386-1391, 10.1073/pnas.1417290112