Overview
This project investigates how chromatin architecture shapes neuronal fitness during development. Using Drosophila genetics, advanced imaging, and chromatin biology, the student will uncover how genome organisation influences neuronal survival and tissue robustness, providing new insights into mechanisms underlying neurodevelopmental disorders.
About this opportunity
Understanding how developing tissues maintain robustness despite genetic perturbations is a central challenge in biology. Cell competition is a key mechanism by which less-fit cells are eliminated to preserve tissue function, yet how neuronal fitness is determined remains poorly understood. Chromatin architectural proteins, such as CTCF, regulate genome organisation and gene expression, and mutations in these factors are increasingly linked to neurodevelopmental disorders. However, how chromatin architecture influences neuronal survival is unknown.
This project will investigate how disruption of chromatin architecture affects neuronal cellular fitness and triggers cell competition during development. Using Drosophila melanogaster as a powerful genetic model, the student will introduce disease-associated mutations in chromatin regulators and assess their impact on neuronal survival, growth, and tissue organisation. Genetic mosaic approaches will enable direct comparison between mutant and wild-type neurons, allowing quantification of competitive interactions, apoptosis, and cellular fitness using confocal microscopy. At the tissue level, three-dimensional micro-computed tomography (micro-CT) will be used to analyse how chromatin perturbations influence brain structure. This integrated approach will link genome architecture to neuronal survival across cellular and tissue scales.
The student will receive interdisciplinary training in developmental genetics, chromatin biology, and advanced imaging. During the first two years at the University of Liverpool, training will focus on Drosophila genetics, cell competition assays, confocal microscopy, and micro-CT imaging. In the final two years at the National Institute of Mental Health and Neurosciences (NIMHANS), the student will develop expertise in chromatin regulatory mechanisms and modelling of disease-associated mutations. This dual PhD programme provides a unique opportunity to gain complementary skills across two internationally recognised research environments.
The project is structured to support both training and independent research. The first year will focus on establishing genetic models and acquiring core experimental skills. The second year will involve functional analysis of chromatin perturbations and neuronal fitness. In the final two years, the student will expand mechanistic investigations, integrate multiscale datasets, and develop an independent research project leading to a PhD thesis. Throughout the programme, the student will benefit from close supervision and collaboration between Liverpool and NIMHANS, fostering an interdisciplinary and international research experience.
Further reading
Clavería C, Torres M.
Cell competition: mechanisms and physiological roles.
https://doi.org/10.1146/annurev-cellbio-111315-125142
Merino MM, Levayer R, Moreno E.
Survival of the fittest: essential roles of cell competition in development, aging, and cancer.
https://doi.org/10.1016/j.tcb.2016.05.009
Merino MM et al.
“Fitness fingerprints” mediate physiological culling of unwanted neurons in Drosophila.
https://doi.org/10.1016/j.cub.2013.05.053
Ong CT, Corces VG.
CTCF: an architectural protein bridging genome topology and function.
https://doi.org/10.1038/nrg3663
Dixon JR et al.
Topological domains in mammalian genomes identified by analysis of chromatin interactions.
https://doi.org/10.1038/nature11082
Gregor A et al.
De novo mutations in the genome organizer CTCF cause intellectual disability.
https://doi.org/10.1016/j.ajhg.2013.05.007