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Click here to search FindAPhD.com for PhD studentship opportunitiesAbout the Project
The impressive range of anatomical variations observed in animals along their body axis is the result of distinct control mechanisms governing gene expression. Central to this process are HOX transcription factors (TFs). Despite their lack of DNA-binding specificity in laboratory settings, HOX proteins direct precise gene expression programs in living organisms.
This raises a baffling question: how do HOX proteins achieve such specificity? To address this fundamental query, we plan to investigate dynamic differentiation models, specifically human embryonic stem cells, using a combination of epigenomic, transcriptomic, and TF binding profiling techniques. Collectively, these approaches will reveal fundamental mechanisms that underlie development, disease, and evolution in vertebrates. Additionally, findings will yield predictive and testable models concerning the functional binding of TFs.
Training/techniques to be provided
The culturing and differentiation of human embryonic stem cells into the cardiac and neural crest lineage.
High-throughput approaches, including ChIP_seq, ATAC-seq, CUT&RUN, transcriptomics.
Genetic engineering techniques including CRISPR/CAS9 genome editing to generate loss-of- and gain-of-function manipulations to understand gene function. General molecular biology techniques including PCR, qPCR, plasmid cloning, immunofluorescence, western blotting and flow cytometry.
Entry Requirements
Candidates are expected to hold (or be about to obtain) a minimum upper second-class honours degree (or equivalent) in a related area / subject. Candidates with experience in developmental biology, control of gene expression or bioinformatics are encouraged to apply.
How to Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the PhD Dentistry.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit https://www.bmh.manchester.ac.uk/study/research/international/
Equality, Diversity & Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website
https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
Funding Notes
Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/
References
Bridoux, L., Zarrineh, P., Mallen, J., Phuycharoen, M., Latorre, V., Ladam, F., Losa, M., Baker, S.M., Sagerstrom, C., Mace, K.A., Rattray, M., Bobola, N. HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation. PLOS Genet. Dec 14;16(12):e1009162 (2020).
Gerrard DT, Berry AA, Jennings RE, Birket MJ, Zarrineh P, Garstang MG, Withey SJ, Short P, Jiménez-Gancedo S, Firbas PN, Donaldson I, Sharrocks AD, Piper Hanley K, Hurles ME, Gomez-Skarmeta JL, Bobola N, Hanley NA. Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders. Nat. Comms. Aug 6;11(1):3920 (2020)
Schwach V, Fernandes MG, Maas S, Gerhardt S, Tsonaka R, van der Weerd L, Passier RP, Mummery CL, Birket MJ*, Salvatori DCF*. Expandable human cardiovascular progenitors from stem cells for regenerating mouse heart after myocardial infarction. Cardiovascular Res. Mar 1;116(3):545-553 (2020). *Authors contributed equally to the work.
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