Impact of DNA replication initiation landscape in generating pancreatic β-cells from stem cells at University of Birmingham on FindAPhD.com

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Dr I Akerman, Prof Thorsten Allers No more applications being accepted Competition Funded PhD Project (Students Worldwide)

Birmingham United Kingdom Bioinformatics Cell Biology Genetics Molecular Biology

About the Project

Collaborator: Dr. Alex Lubbock Alex, Rosalind Franklin Institute

Interested in gene regulation and the cell cycle? Find stem cells fascinating? Please read on!

Our laboratory is focused on regenerative therapies that aim to treat diabetes with stem cell-derived pancreatic beta cells. We are one of the handful of laboratories that has established generation of pancreatic beta cells in both 2D and 3D culture systems in the UK. In brief, we study how the two fundamental processes in the cell, transcription and DNA replication, impact each other… We are looking for an enthusiastic PhD student to join our vibrant research team to work on how DNA replication and the cell cycle impact transcription and cell fate in our state of the art stem cell to beta cell differentiation protocol. This project will be an interdisciplinary project where the student will have the opportunity to work with stem cell and genomics experts from University of Birmingham (Dr Ildem Akerman and Fiona Docherty), DNA replication experts from Nottingham (Prof Thorsten Allers) and computational experts MRC AIM DTP – Akerman from Rosalind Franklin Institute (Dr. Alex Lubbock). At the end of her/his PhD, our student would have acquired a wide range of molecular and computational biology skills, as well as sought after expertise in stem cell biology.

How to apply

Informal enquiries should be directed to Dr Ildem Akerman [Email Address Removed]

To apply, please download the application form and complete all documentation available at https://more.bham.ac.uk/mrc-aim/phd-opportunities/ and send completed applications to [Email Address Removed]

The deadline for submitting applications is 09:00 GMT Monday 16 January 2023. Please ensure that your application is submitted with all required documentation as incomplete applications will not be considered.

References

1. Global Report on Diabetes, World Health Organization (2016).
2. de Klerk, E. & Hebrok, M. Stem Cell-Based Clinical Trials for Diabetes Mellitus. Front Endocrinol (Lausanne) 12, 631463 (2021).
3. Pauklin, S. & Vallier, L. The cell-cycle state of stem cells determines cell fate propensity. Cell 155, 135-47 (2013).
4. Akerman, I. et al. A predictable conserved DNA base composition signature defines human core DNA replication origins. Nat Commun 11, 4826 (2020).
5. Akerman, I. et al. Neonatal diabetes mutations disrupt a chromatin pioneering function that activates the human insulin gene. Cell Rep 35, 108981 (2021).
6. Akerman, I. et al. Human Pancreatic beta Cell lncRNAs Control Cell-Specific Regulatory Networks. Cell Metab 25, 400-411 (2017).
7. Allen, H.L. et al. GATA6 haploinsufficiency causes pancreatic agenesis in humans. Nat Genet 44, 20-22 (2011).
8. Arnes, L., Akerman, I., Balderes, D.A., Ferrer, J. & Sussel, L. betalinc1 encodes a long noncoding RNA that regulates islet beta-cell formation and function. Genes Dev 30, 502-7 (2016).
9. Garin, I. et al. Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis. Proc Natl Acad Sci U S A 107, 3105-10 (2010).
10. Moran, I. et al. Human beta cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes. Cell Metab 16, 435-48 (2012).
11. Pasquali, L. et al. Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants. Nat Genet 46, 136-143 (2014).
12. Bazarova, A., Nieduszynski, C.A., Akerman, I. & Burroughs, N.J. Bayesian inference of origin firing time distributions, origin interference and licencing probabilities from Next Generation Sequencing data. Nucleic Acids Res 47, 2229-2243 (2019).
13. Ganier, O., Prorok, P., Akerman, I. & Mechali, M. Metazoan DNA replication origins. Curr Opin Cell Biol 58, 134-141 (2019)

Where will I study?

University of Birmingham

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