Tina Zajec Hudnik

In the central nervous system, the activation products of the classical and alternative complement pathway participate in synaptic pruning. While the removal of inappropriate synaptic connections is essential during development, increased complement activity in neuropsychiatric disorders, such as major depressive disorder, bipolar disorder, schizophrenia, etc., may drive excessive elimination of otherwise healthy synapses.

Within the iCNS consortium I collaborate with Jessica Hoang and Marta Mota to develop and test tools for visualizing complement activity in the brain. We will combine the advantages of activity-based probes with modularity of nanobodies and protein binders, the latter is the focus of my PhD project. With this approach we aim to distinguish between inactive complement components and the physiologically more relevant active ones, a distinction that cannot be made with currently available tools. By using a combination of biophysical and structural biology techniques such as X-ray crystallography and cryo-electron microscopy I will characterize and validate these tools. Ultimately, we would like to use them, to gain deeper insight into the molecular mechanisms underlying complement activity in neuropsychiatric disorders.

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