Dissecting the function of PRR12 and its role in Neuroocular Syndrome through a multi-omic approach

This project has been approved for funding - the activation procedure is still pending

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2023

The main aim of this research project is to understand the molecular mechanisms underlying the neuro-ocular syndrome (NOC), a disease mainly characterized by neurodevelopment impairments and often associated with variable structural eye defects of variable severity. NOC is a recently identified genetic disease associated with mutations in the PRR12 gene. Unfortunately, very little is known about this gene except that it is highly expressed in brain and eye neurons and that the encoded protein has a nuclear localization and could bind DNA. Given these data, we have organized our proposal into three main aims. Firstly, we will study PRR12 transcript(s) from blood cells of NOC individuals to clarify the effects of the identified variants on PRR12 expression. Secondly, we will use genomic editing technologies to generate neuronal cells carrying some of the PRR12 mutations previously identified in patients. These cellular models will help determine the impact of such mutations in cell biology.  Finally, we will employ upfront “omic” technologies to determine whether PRR12 binds DNA and where this occurs in our genome, in order to understand the function of PRR12 in the nucleus. The role of PRR12 will be further clarified by the identification of nuclear proteins interacting with it. The identification of PRR12's "friends" will allow to understand the biological context where it operates.

Overall, a better understanding of the physiological role of PRR12 and the molecular mechanisms by which PRR12 variants cause NOC will pave the way for possible treatments, thus offering future therapeutic hope to patients.