Bachelor and Master theses

Further opportunities

Master thesis on
modeling the neuroactive forms of osteocalcin

Osteocalcin is a small, disordered protein secreted by osteoclasts, with an emerging role inthe bone-brain axis. It can be carboxylated at three glutamate side chains. Its carboxylated form mainly acts in bone mineralization, while its undercaboxylated species exerts endocrine functions. In particular, undercaboxylated osteocalcin acts on the central nervous system through the G protein-coupled receptors GPR158 and GPR37, playing a role in cognition, memory, emotion, and neurodegeneration.

This project aims at characterizing the effects of carboxylation and calcium binding on osteocalcin conformational properties under the conditions employed for native mass spectrometry, a powerful tool for investigating heterogeneous and dynamic systems. Such an approach is based on an established collaboration between the computational group of Prof. Paolo Carloni in Juelich and the experimental group of Prof. Rita Grandori in Milan, and has been already applied to modeling proteins with different degrees of structural disorder. It is of interest to apply this approach to the investigation of this intrinsically disordered protein with a complex biological role.

We are looking for highly motivated individuals with an interest in neurosciences, molecular simulations and biophysics. The research will be held in close collaboration with the experimental lab of Prof. Rita Grandori at the University of Milano-Bicocca, Italy.

Contacts: p.carloni@fz-juelich.de and rita.grandori@unimib.it

References

• Ami et al. 2024, J Am Chem Soc 146, 27755-27769. doi: 10.1021/jacs.4c09732
• Li et al. 2017, J Phys Chem Lett 8, 1105-1112. doi: 10.1021/acs.jpclett.7b00127
• Li et al. 2016, Mass Spectrom Rev 35, 111-122. doi: 10.1002/mas.21465
• D’Urzo et al 2015, J Am Soc Mass Spectrom 26, 472-481. doi: 10.1007/s13361-014-1048-z
• Marchese et al. 2012, J Am Soc Mass Spectrom 23, 1903-10. doi: 10.1007/s13361-012-0449-0