Dr. Xiao Jakob Schmitt
Molecular investigation of the SNARE Complex Formation Machinery in the context of SNAREopathic Mutations
Biochemistry
Postdoc
Protein Biochemistry
14195 Berlin
Fast and reliable neurotransmission is fundamental to how we think, feel, and respond to the world around us. In chemical synapses, this process depends on the precise exocytotic fusion of synaptic vesicles at the presynaptic membrane, enabling the release of neurotransmitters. This fusion is driven by the assembly of the SNARE complex, a four-helix bundle composed of Syntaxin-1, Synaptobrevin-2, and SNAP-25, which pulls the vesicle and presynaptic membranes together through a zippering mechanism. The formation of the SNARE complex is a multistep, tightly regulated process coordinated by orchestrating proteins such as Munc18-1 (STXBP1) and Munc13-1. Despite its complexity, this machinery lacks redundancy. As a result, mutations in SNARE complex components often lead to a range of severe neurological disorders collectively referred to as SNAREopathies. Yet, the exact molecular details of SNARE complex assembly, and how disease-causing mutations disrupt it, remain incompletely understood. Our research aims to dissect the molecular mechanism of SNARE complex formation by using SNAREopathic mutations as tools to probe the interactions between core and regulatory proteins. Through this approach, we seek to uncover the fundamental principles of synaptic vesicle fusion and its failure in disease.
After completing his Abitur at the Innerstädtisches Gymnasium in Rostock, Xiao Jakob Schmitt pursued a teaching degree in Chemistry and Biology at Freie Universität Berlin. During his undergraduate and graduate studies, he worked as a student assistant in the research groups of Prof. Kevin Pagel (Freie Universität Berlin) and Prof. Gert von Helden (Fritz Haber Institute of the Max Planck Society), where he investigated protein structures and interactions using native ion mobility–mass spectrometry. Data from his bachelor’s and master’s theses contributed to publications in their respective fields. Driven by a growing interest in protein biochemistry, he joined the lab of Prof. Christian Freund at Freie Universität Berlin for his doctoral studies, where he earned his Dr. rer. nat. degree. His PhD research focused on the molecular mechanisms of SNARE complex assembly, particularly in the context of disease-associated SNAREopathic mutations. Xiao Jakob Schmitt is currently a postdoctoral researcher working under Prof. Christian Freund and Prof. Nevan Krogan (University of California, San Francisco) as part of the Einstein Visiting Fellowships program. His research focuses on unravelling the molecular mechanism of the SNARE complex formation machinery in the context of neurological disorders, using a combination of biochemical, structural, and functional approaches.
(1) Miriam Bertazzon, Almudena Hurtado-Pico, Carlos Plaza-Sirvent, Marc Schuster, Marco Preußner, Benno Kuropka, Fan Kiu, Andor Zenon Amandus Kristen, Xiao Jakob Schmitt, Benjamin König, Miguel Álvaro-Benito, Esam T. Abualrous, Gesa I. Albert, Stefanie Kliche, Florian Heyd, Ingo Schmitz, Christian Freund. The nuclear GYF protein CD2BP2/U5–52K is required for T cell homeostasis, 2024; Frontiers in Immunology, 15, 1415839.
(2) Fabio Lolicato, Julia P. Steringer, Roberto Saleppico, Daniel Beyer, Jaime Fernandez‑Sobaberas, Sebastian Unger, Steffen Klein, Petra Riegerová, Sabine Wegehingel, Hans‑Michael Müller, Xiao Jakob Schmitt, Shreyas Kaptan, Christian Freund, Martin Hof, Radek Šachl, Petr Chlanda, Ilpo Vattulainen, Walter Nickel. Disulfide bridge-dependent dimerization triggers FGF2 membrane translocation into the extracellular space, 2024; eLife, 12, RP88579.
(3) Gülçin Vardar*, Fabian Gerth*, Xiao Jakob Schmitt, Pia Rautenstrauch, Thorsten Trimbuch, Julian Schubert, Holger Lerche, Christian Rosenmund, Christian Freund. Epilepsy-causing STX1B mutations translate altered protein functions into distinct phenotypes in mouse neurons, 2020; Brain, 143 (7): 2119-2138.
(*These authors contributed equally to this work)
(4) Fabian Gerth, Maria Jäpel, Jana Sticht, Benno Kuropka, Xiao Jakob Schmitt, Jan H. Driller, Bernhard Loll, Markus C. Wahl, Kevin Pagel, Volker Haucke, Christian Freund. Exon Inclusion Modulates Conformation Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain, 2019; Structure, 27 (6): 977-987.
(5) Melanie Göth, Frederik Lermyte*, Xiao Jakob Schmitt*, Stephan Warnke, Gert von Helden, Frank Sobott, Kevin Pagel. Gas-Phase microsolvation of ubiquitin: investigation of crown ether complextation sites using ion mobility-mass spectrometry, 2016; The Analyst, 141 (19): 5502-5510. (*These authors contributed equally to this work)
Keywords
- Neuron, Synapse, SNARE, STX1, STXBP1 (Munc18-1), Munc13-1, MUN Domain, SNAREopathy, SNAREopathic Mutation, Epilepsy, Autism Disease