Chari, Ashwin, Dr. rer. nat.

Research Group for Structural Biochemistry and Mechanisms

2004 Diploma (Biochemistry, Molecular Biology and Biophysics) ETH Zürich
2009 Dr. rer. nat., Julius-Maximilian University Würzburg
2009 – 2011 Postdoc and Project Leader Julius-Maximilian University of Würzburg, Department of Biochemistry
2011 – 2016 DFG Project Leader in the Research Group for 3D Cryo-Electron Microscopy, MPI-BPC Göttingen
2016 – 2020 Project Group Leader in the Department of Structural Dynamics, MPI-BPC Göttingen
Since July 2020 Research Group Leader, Research Group for Structural Biochemistry and Mechanisms, MPI-NAT Göttingen

Major Research Interests

The recent years of whole genome studies have enforced a view, in which most cellular constituents do not act in isolation, but as part of large assemblies. A large spectrum of biological reactions and tasks essential for the survival of cells are performed by these macromolecular complexes, also referred to as molecular machines. These biochemically labile assemblies are composed of either protein only, or proteins bound to nucleic acids (DNA or RNA). Prominent examples are the proteasome, the fatty acid synthase, the nucleosome, the ribosome and the spliceosome. As cellular homeostasis is governed by macromolecular complex function, their mis-function is also a central cause for human disease, making the in-depth study of functional mechanisms essential for the investigation of disease etiology.
In our research we apply mechanistic biochemistry and structural biology to study large macromolecular complexes involved in proteostasis and fatty acid metabolism. Owing to the labile nature and complexity of interrogating these molecular machines, we are engaged in the development of biochemical tools to purify, stabilize and arrest them in distinct functional states. We also develop methods for X-ray data collection, phasing, structure determination and refinement of atomic models of large complexes, as well as apply time-resolved structural biology approaches to study dynamic aspects of macromolecular complex function.

Homepage Department/Research Group

https://www.mpinat.mpg.de/chari

Selected Recent Publications

Chari A , Golas MM, Klingenhager M, Neuenkirchen N, Sander B, Englbrecht C, Sickmann A, Stark H, Fischer U. An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs. Cell (2008), 135:497-509.

Chari A , Haselbach D, Kirves JM, Ohmer J, Paknia E, Fischer N, Ganichkin O, Möller V, Frye JJ, Petzold G, Jarvis M, Tietzel M, Grimm C, Peters JM, Schulman BA, Tittman K, Markl J, Fischer U, Stark H. ProteoPlex: stability optimization of macromolecular complexes by sparse- matrix screening of chemical space. Nat Methods. (2015) 12: 859-865Chari A, Haselbach D, Kirves JM, Ohmer J, Paknia E, Fischer N, Ganichkin O, Möller V, Frye JJ, Petzold G, Jarvis M, Tietzel M, Grimm C, Peters JM, Schulman BA, Tittman K, Markl J, Fischer U, Stark H. ProteoPlex: stability optimization of macromolecular complexes by sparse- matrix screening of chemical space. Nat Methods. (2015) 12: 859-865

Schrader J, Henneberg F, Mata R, Tittmann K, Schneider TR, Stark H, Bourenkov G, Chari A . The inhibition mechanism of human 20S proteasomes enables next-generation inhibitor design. Science (2016), 353: 594-598

Haselbach D, Schrader J, Lambrecht F, Henneberg F, Chari A , Stark H. Long-range allosteric regulation of the human 26S proteasome by 20S proteasome-targeting drugs. Nat Commun. 2017, 8: 15578-15585

Singh K, Graf B, Linden A, Sautner V, Urlaub H, Tittmann K, Stark H, Chari A . Discovery of a Regulatory Subunit of the Yeast Fatty Acid Synthase. Cell 2020, 180: 1130- 1143

Yip KM, Fischer N, Paknia E, Chari A , Stark H. Atomic-resolution protein structure determination by cryo-EM. Nature 2020, 587: 157- 161