Objective Synapses, connections between neurons, are critical to the formation of neural circuits. Functional neural circuits control intricate processes such as learning and memory, whereas failure in neural circuitry formation can lead to developmental disorders including autism.At the molecular level, synapse formation is enabled by cell-adhesion molecules that interact across the synapse. At present, many individual proteins have been identified that contribute to synaptic cell adhesion, but it is unclear how these individual proteins team up in macro-molecular complexes. I will focus on synaptic cell-adhesion complexes containing Teneurins, a protein family whose essential role in synapse formation has only recently been characterized.To understand how Teneurin complexes promote synapse formation, I aim to determine the molecular mechanisms that underlie Teneurin1 and Teneurin2 dimerization, including complex formation with their recently identified binding partner Latrophilin. To achieve this goal, I will determine the structure of Teneurin protein complexes using single particle electron cryo-microscopy. In parallel, I will study the function of Teneurin complexes in synapse formation using primary hippocampal neurons. Dissecting the molecular mechanisms that underlie Teneurin functions might ultimately advance small molecule therapeutics to treat developmental diseases, including autism.The work I propose here, draws upon my background in the field of developmental neurobiology, but complements that background with new knowledge and skill sets in structural biology to set me off conducting my own line of research as an independent scientist. Fields of science natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologynatural sciencesphysical sciencesopticsmicroscopyelectron microscopynatural sciencesbiological sciencesmolecular biologystructural biology Keywords Cell adhesion Macro-molecular complexes Synapse Single particle electron cryo-microscopy Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2015 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator UNIVERSITEIT UTRECHT Net EU contribution € 165 598,80 Address HEIDELBERGLAAN 8 3584 CS Utrecht Netherlands See on map Region West-Nederland Utrecht Utrecht Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 165 598,80
