Usman Mukhtar
Academic and Work Experience Prior to Sept 2024 Programme Start
I completed an MSci in Cell Biology at University College London in 2024. During my degree, I undertook a seven-week summer internship in 2023 at the University of Oxford’s Dunn School of Pathology in the Esashi Lab, investigating the role of DNA topoisomerase IIβ (TOP2B) in cellular quiescence. For my final-year project in the Pichaud Lab at the LMCB, I studied how basement membrane components, particularly Laminin, regulate proliferation and organ size during development, using the Drosophila retina as a model system.
PhD Programme- Year 1- MRes and Project Rotations
Rotation Project:
Developing in vitro models of normal and pathological trophoblast development using human embryonic stem cell (hESC) and human trophoblast stem cell (hTSC) lines (Fogarty Lab).
Investigating key signalling pathways (Sonic hedgehog and FGF) that regulate temporomandibular joint (TMJ) development and homeostasis in mouse models (Tucker Lab).
Visualising FOXG1 cleavage and subcellular localisation in vivo during neurodevelopment using zebrafish models (Houart Lab).
PhD Programme- Years 2 to 4- Doctoral Studies
My PhD project focuses on the transcription factor FOXG1, which plays an essential role in early forebrain development by regulating neural progenitor proliferation, patterning, and neuronal differentiation. In addition to its well-established nuclear functions, FOXG1 is known (albeit to a lesser extent) to undergo proteolytic cleavage, generating a C-terminal fragment that translocates to mitochondria. Recent evidence from our lab suggests that this fragment supports mitochondrial function by modulating oxidative phosphorylation and promoting excitatory neuron differentiation. Dysregulation of this cleavage process appears to contribute to the pathology of FOXG1 syndrome, a severe neurodevelopmental disorder. However, when and where FOXG1 cleavage occurs during development, and how this process is regulated, remain largely unknown.
The first aim of my project is to define the spatio-temporal dynamics of FOXG1 cleavage during neurodevelopment using zebrafish as a model system. Building on this, my second aim is to identify the FOXG1 cleavage site and the protease responsible, both of which are currently unknown. Finally, my third aim is to uncover the upstream regulatory mechanisms that control FOXG1 cleavage during development.
