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Mechanisms of gene regulation shared between human development and neurodegeneration

   Department of Life Sciences

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  Dr Marco Trizzino  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Applications are invited for a research studentship leading to the award of a PhD degree, under the supervision of Dr. Marco Trizzino, to investigate mechanisms of gene regulation shared between human development and neurodegeneration.

The determination of cell fate is a complex developmental process which requires fine-tuned timely activation and repression of developmental genes. This process (“developmental gene regulation”) is regulated by an elaborated machinery which includes non-coding DNA regulatory elements (enhancers, promoters), DNA binding proteins (transcription factors), and chromatin associated protein complexes, whose role is to remodel nucleosome positioning to make the chromatin open and accessible for the binding of transcription factors and other co-factors. Defects at any level in this complex machinery affect the timing and the extent of the expression of the developmental genes, and this usually leads to impaired developmental processes, resulting in developmental syndromes.

In our lab we leverage a specific type of stem cells (induced Pluripotent Stem Cells, or “iPSCs”) and we differentiate them into neural crest cells and neurons to model craniofacial and neural development, and investigate the function of genes recurrently mutated across human developmental syndromes. On the differentiated cells we perform a wide array of genomic assays (e.g. RNA-seq, ChIP-seq, ATAC-seq) and biochemical approaches to unveil the function of the mutated genes (and associated proteins). Importantly, mounting evidence is suggesting that neurodevelopment and neurodegeneration are strongly linked, and that the neurodegenerative phenotypes arise early in life at the cellular level as a consequence of impaired development. We are keen on investigating this, particularly in the context of Alzheimer’s Disease.

The PhD student will choose a project along the above-described lines of research. The project will be centered on iPSC differentiation and developmental genomics, with both an experimental (i.e. “wet-bench”) and a computational component. The PhD student will receive training in cell culture, stem-cell differentiation, genomics and biochemistry. We perform all the computational analyses of the genomic data that we generate, therefore the student will receive training in this important aspect of the research as well.

In addition, the PhD student will learn a range of biochemical methods such as co-immunoprecipitation and mass-spectrometry.

Requirements and eligibility

The studentship provides 3 years of funding starting January 2023 (or soon thereafter).  Applicants should have a BSc honours degree (at least 2.1 or equivalent) in Biology, Biochemistry, Genetics or a related discipline. Applicants with a Masters degree (at Merit level or better) in addition to the BSc will be given preference. Interdisciplinarity may be given preference. Intellectual ability, enthusiasm and self-motivation are essential.

How to apply: 

Please direct informal enquiries and requests for further information to Dr. Marco Trizzino ([Email Address Removed]). Please email a single PDF file including: a brief cover letter describing your relevant interests and research experience, your C.V. and names and contact information of three referees. Applications will be considered as they are received, so early applications are encouraged.

Funding Notes

The post is supported by a bursary and fees (at the UK student rate only) funded by the Alzheimer’s Association. The studentship is for 36 months from January 2023 (or soon thereafter).
Funding provides full support for tuition fees for the three-year duration of the studentship, and an annual tax-free stipend of £19,668 per year.
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