Details
Aquatic vertebrates such as amphibians and fish are able to regenerate complex structures including limb, tail, spinal cord, retina and heart. When comparable damage occurs in mammals, tissue fails to regrow and scarring occurs. A major question for regenerative biology is how are regenerative cells recruited to sites of injury. Our labs use zebrafish tail regeneration to better understand these processes. We have recently identified a member of the TGFbeta superfamily that is a recruitment signal for regenerative cells. Our analysis using bulk RNA-seq and scRNA-seq has identified previously unknown sub-populations of cells that are able to respond to this recruitment signal. This project aims to determine how and why these cells respond to TGFbeta signalling. The successful candidate will utilize high content light-sheet microscopy, genetic and pharmacological manipulation and scRNA-seq analysis to address this question. This basic research project may be used in the future to develop methods to recruit pro regenerative cells to sites of injury in human patients.
References: Tzunget al. Nature, 618(7965):543-549 (2023); Romero et al. Nature Comms 9:4010(2018); Roehl. Int. J. Dev. Biol. 62:473(2018)
About the DTP
This studentship is offered as part of the White Rose BBSRC Doctoral Training Partnership (DTP) in Mechanistic Biology, which brings together the research of the world-class molecular and cellular bioscience centres at the White Rose universities of Leeds, Sheffield and York.
Our mission is to train excellent bio-scientists who understand how living systems work
and can innovate to address global challenges, such as the impact of climate change, a healthier old age, sustainable food production, land use and energy production.
What is on offer?
This is a core studentship for entry in October 2024.
Join us and you will receive a 4-year, funded PhD programme of research and skills training, with cross-disciplinary supervision, plus a structured programme of cohort-wide training and networking events. A highlight is the annual symposium, which is planned and delivered by students.
A unique part of your training will be the Professional Internships for PhD Students (PIPS), where you will spend three months at a host organisation of your choosing, gaining experience of work in a professional environment, and acquiring transferable skills that will be beneficial in your future career.
How to apply – Expression of Interest
Students may apply for up to three projects anywhere in the Doctoral Training Partnership (DTP). Applications will be to the DTP centrally, using an online Expression of Interest (EoI). The EoI will include:
§ CV information; not submitted separately
§ Equality, Diversity and Inclusion (EDI) data
§ Names of two referees
Deadline for EoIs is midnight Sunday 7th January 2024.
Submit EoIs using this link: https://leeds.onlinesurveys.ac.uk/white-rose-bbsrc-dtp-expression-of-interest-form
Shortlisted candidates will be required to make formal applications to the Graduate School at each institution, supplying the necessary paperwork.
Interviews will be held either Friday 2nd and Monday 5th to Friday 9th February, or Monday 19th to Friday 23rd and Monday 26th February 2024, in-person at Leeds, Sheffield and York, with a panel representing all 3 Universities. Shortlisted candidates will be notified of a specific time/date to attend. If you have applied for more than one project and are selected for interview, you will be interviewed only once.
Website: https://www.whiterose-mechanisticbiology-dtp.ac.uk/
Funding Notes
Appointed candidates will be fully funded for 4 years:
Tax-free annual stipend at the UKRI rate. The rate for starters in 2023/24 was £18,622. (Rates for 2024/25 starters are not yet available).
UKRI tuition fees – These are paid directly to the host institution.
A Research Training and Support Grant
An allowance for Fieldwork/Conference/Travel
A Professional Internship for PhD Students (PIPS) allowance
Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive
References
Tzunget al. Nature, 618(7965):543-549 (2023); Romero et al. Nature Comms 9:4010(2018); Roehl. Int. J. Dev. Biol. 62:473(2018).
1) A median fin derived from the lateral plate mesoderm and the origin of paired fins. Tzung, Lalonde, Prummel, Mahabaleshwar, Hannah, Stundl, Cass, Le, Lea, Dorey, Tomecka, Zhang, Brombacher, White, Roehl, Tulenko, Winkler, Currie, Amaya, Davis, Bronner, Mosimann, Carney. Nature, 618(7965):543-549 (2023)
2) Tomecka MJ, Ethiraj LP, Sanchez LM, Roehl HH, and Carney TJ. Clinical pathologies of bone fracture modelled in zebrafish. Dis Model Mech, 12: dmm037630 (2019)
3) Roehl HH. Linking wound response and inflammation to regeneration in the zebrafish larval fin. Int J Dev Biol 62, 473-477 (2018)
4) Romero MMG, McCathie G, Jankun P, Roehl HH. Damage-induced reactive oxygen species enable zebrafish tail regeneration by repositioning of Hedgehog expressing cells. Nat Commun 9: 4010 (2018)
Khalil MI, Ismail HM, Panasyuk G, Bdzhola A, Filonenko V, Gout I, Pardo OE. Asymmetric Dimethylation of Ribosomal S6 Kinase 2 Regulates Its Cellular Localisation and Pro-Survival Function. Int J Mol Sci. 2023 May 15;24(10):8806. doi: 10.3390/ijms24108806. PMID: 37240151; PMCID: PMC10218830.
• Zhu L, Kamalathevan P, Koneva LA, Zarebska JM, Chanalaris A, Ismail H, Wiberg A, Ng M, Muhammad H, Walsby-Tickle J, McCullagh JSO, Watt FE; Oxford Hand Surgical Team; Sansom SN, Furniss D, Gardiner MD, Vincent TL, Riley N, Spiteri M, McNab I, Little C, Cogswell L, Critchley P, Giele H, Shirley R. Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis. Sci Transl Med. 2022 Dec 21;14(676):eabm4054. doi: 10.1126/scitranslmed.abm4054. Epub 2022 Dec 21. PMID: 36542696.
• Kaokhum N, Pinto-Fernández A, Wilkinson M, Kessler BM, Ismail HM*. The Mechano-Ubiquitinome of Articular Cartilage: Differential Ubiquitination and Activation of a Group of ER-Associated DUBs and ER Stress Regulators. Mol Cell Proteomics. 2022 Dec;21(12):100419. doi: 10.1016/j.mcpro.2022.100419. Epub 2022 Sep 28. PMID: 36182100; PMCID: PMC9708921.
• Southan J., McHugh E., Walker H., Ismail HM*. Metabolic signature of articular cartilage following mechanical injury: An integrated transcriptomics and metabolomics analysis. Front. Mol. Biosci (2020). doi: 10.3389/fmolb.2020.592905.