Nemanja Vasovic
Academic and Work Experience Prior to Sept 2023 Programme Start
I obtained a bachelor’s degree in Molecular Biology and Physiology from the University of Belgrade, followed by a master’s degree in Human Biology from Ludwig Maximilian University of Munich (LMU). During my time at LMU, I completed my thesis project in Mirjana Kessler’s lab, where I worked on in vitro modelling of carboplatin response in high-grade serous ovarian cancer patient-derived organoids. Afterward, I joined a biotech startup in Munich, where I spent a year working on novel AAV gene therapies for retinal diseases.
PhD Programme- Year 1- MRes and Project Rotations
During the first year of the “Advanced Therapies for Regenerative Medicine” programme, I completed three lab rotations:
1st Rotation (Prof. Rachael Pearson's Lab): I worked on developing microfluidic chip-based photoreceptor cultures for the screening and identification of neurite guidance cues.
2nd Rotation (Dr. Ciro Chiappini): I became familiar with nanoneedle technology and worked on developing a nanoneedle platform for delivering gene editing tools to corneal endothelial cells.
3rd Rotation (Dr. Alessandra Vigilante and Prof. Andrea Streit): Here, I conducted single-cell RNA sequencing analysis of early human inner ear cells, aiming to identify and annotate the different cell types that arise during the development of this organ.
PhD Programme- Years 2 to 4 - Doctoral Studies
The Pearson/Ali group has developed a protocol for generating human pluripotent stem cell (hPSC)-derived retinal organoids (hROs) that contain both cone and rod photoreceptors. These cells can be isolated using various cell sorting methods, relying on well-defined surface markers for rods and cones. The isolated immature human cone (hCone) photoreceptors are then transplanted into mouse models, where they have been shown to form new synaptic connections within the host retina, based on the localisation of known pre- and post-synaptic marker.
In this project, I seek to characterize the restored neuronal connectome to better understand the quality of sight restored to patients, and to explore ways to promote greater efficiency of synapse formation between donor photoreceptors and target neurons in the recipient retina. I will employ synaptic viral tracing techniques combined with RNA sequencing (RNAseq) to probe the retinal transplant connectome and better understand what makes some donor photoreceptors connect and other fail. Furthermore, I will optimise a prototype microfluidic cell culturing platform to develop an in vitro photoreceptor/inner retina synapse model system to test candidate molecules that might promote functional connectivity in vivo, specifically investigating the role of Wnt9a, a candidate axon guidance molecule, in the formation of PR-BC synapses. Finally, to provide a target neutral approach to modifying plasticity, I will explore the potential for promoting functional integration of transplanted cone photoreceptors into the diseased retina using environmental enrichment.
Defining the restored connectome is fundamental to our understanding of how and to what extent photoreceptor transplantation therapy can restore normal vision. Furthermore, developing platforms to help identify molecules that promote human photoreceptor synapse formation offers the potential to substantially improve our understanding of human retinal synapse formation.
