Project:
High Resolution Mapping of Transcription Factors During Neurodevelopment
Laboratories:
Omar Abudayyeh, Ph.D. & Jonathan Gootenberg, Ph.D. and Guoping Feng, Ph.D.
Biographical Information:
Chris received his BSc and MSc from the University of Leicester (UK) in Molecular Genetics. In June 2022, he received his PhD in Molecular Neuroscience from the Medical University of Vienna (Austria), after working at the Center for Molecular Medicine (CeMM) and Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD). During his doctoral work, Chris studied rare neurodevelopmental disorders, identifying and functionally characterizing novel genes involved in human neurodevelopment.
Current Work:
Transcription factors (TFs) control gene expression and are critical regulators of cell state in neurodevelopment and disease. TFs and their gene regulatory networks are notoriously difficult to monitor or manipulate due to a lack of effective tools, such as small molecules, antibodies and genome editing technologies. In the present proposal, we will leverage recent advances in genome engineering technologies to precisely insert a large, multi-domain tag to numerous TFs that function in neurodevelopment. This tag will allow us to manipulate and record various TFs identified in human NDDs and known to function during neurodevelopment. We will combine rapid TF degradation with kinetically matched readouts to assess the primary effects of TF perturbation and build a gene-regulatory map of transitioning cells states, utilizing models of neurodifferentiation. We will examine novel aspects of TF dynamics, providing potentially clinically relevant insights into basic TF biology in neurodevelopment and mechanisms by which NDDs arise that may inform on future therapeutic opportunities.
Keywords:
Genome engineering, transcription factors, autism, neurodevelopment