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  Chromatin remodelling complexes in human brain development


   Faculty of Life Sciences & Medicine

  Dr Cristina Dias, Dr Joseph Atherton  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Chromatin regulators are a group of proteins that control the way the rest of the genome is opened up and “read” by the cellular machinery, with fundamental roles in development and disease. BAF swi/snf complexes are large multiprotein complex chromatin regulators that are some of the most frequently mutated in neurodevelopmental disorders. These complexes incorporate different subunits depending on cellular and developmental context.

The project will use cutting-edge molecular, proteomic and cell biology methods and single-particle cryo-electron microscopy to investigate BAF swi/snf complexes in in vitro models of neurodevelopment.

The student will gain proficiency in molecular and proteomic techniques, cell biology, neurodevelopment and advanced imaging techniques. Involving interdisciplinary collaboration, the project will contribute to the understanding of chromatin regulation in neurodevelopment, with potential for basic science clinical applications.

The project will be carried out through the following aims:

Aim 1: Establish a human in vitro model of progenitor to neuron transition using human induced pluripotent stem cells (iPSCs). The student will employ a combination of microscopy, transcriptomic analysis, and proteomic techniques to define enriched populations of neural progenitors and neurons, capturing the distinct stages of neurodevelopment.

Aim 2: Perform structural characterisation of BAF subunits at different stages of neurodevelopment. Building upon the established model, the student will adopt a multidisciplinary approach to identify time-specific subunits. This will involve the structural determination of immunoprecipitated complexes using cryo-EM, alongside orthogonal validation approaches such as mass spectrometry, density sedimentation, and western blot analysis.

Aim 3: Investigate the interacting proteins with the BAF complex. The student will explore the network of proteins that interact with BAF complexes during neurodevelopment, utilizing proteomic methods to identify and characterize these interactions. This analysis will provide insights into the functional associations and potential regulatory mechanisms involving BAF complexes.

By pursuing these aims, the project aims to shed light on the intricate dynamics of BAF swi/snf complexes during human neurodevelopment, leveraging cutting-edge techniques to unravel the subunit composition, structural organization, and interacting partners of these complexes. The outcomes of this research will contribute to our understanding of the molecular mechanisms underlying neurodevelopmental disorders and provide valuable insights into the role of chromatin regulators in neurodevelopment. Furthermore, the student will acquire a diverse skill set encompassing advanced molecular and proteomic techniques, cell biology, microscopy, transcriptomics, cryo-EM, and data analysis, empowering them to become proficient researchers in the field of neurodevelopment and chromatin regulation.

Academic requirement:

Minimum Upper Second (above 60%) BSc degree in a Life Sciences subject e.g. biomedical sciences or an MSc in a relevant area.

Band D

IELTS 6.5 overall with a minimum of 6.0 in each skill

Or equivalent Band D seen here: English Language Requirements:

Applications

Initial enquires should be made directly with supervisors.

Dr Cristina Dias -

Dr Joseph Atherton -

Biological Sciences (4) Medicine (26)

Funding Notes

Research costs are provided for the PhD project.