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  Using transgenic reporter zebrafish and biomechanical modelling to understand the causes of vertebral malformations


   School of Physiology, Pharmacology & Neuroscience

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  Prof C L Hammond, Prof K Robson-Brown  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

Farmed fish have a very high incidence of skeletal malformations, estimated between 40-65% of all farmed fish. These malformations have implications for the welfare of the fish, but also economically. Surprisingly, little is currently known about the molecular events that lead to skeletal malformations, partially due to a lack of tools allowing the skeletal system to be observed over time, but we predict that, as in humans, a combination of genetics and biomechanical factors are likely to underlie the pathology.
We have put together an interdisciplinary team to tackle this issue using a novel set of tools. Zebrafish have been used extensively as an animal model for developmental and genetic studies, and are increasingly used to give insight into human skeletal disorders. Surprisingly, however, there have been few studies using them as a model for questions relating to other fish species.
We plan to use the dynamic imaging and genetic tools available in zebrafish to begin to probe what underpins the frequent skeletal defects seen in farmed fish like salmon and trout. The project will be co-ordinated between host labs with complementary expertise in genetics and live imaging, and computational biomechanical modelling. The project will give training in cutting edge imaging techniques including microCT, second harmonic generation using multiphoton microscopy, live confocal imaging of transgenic reporter zebrafish. The interdisciplinary nature of the PhD will give the student a highly desirable skill set applicable to a career in many fields. There may also be the opportunity to spend time at Nofima in Norway during the project.

To apply for a SWBio DTP project at the University of Bristol, you need to choose: Faculty of Biomedical Sciences under the ’Faculty’ section, and South West Biosciences Doctoral Training Partnership (PhD) under the ’programme choice’ section. Additionally under the ’Research Details’ section, please indicate that you are applying for a SWBio DTP funded project and give the project title and names of supervisors. For eligibility information: http://www.bristol.ac.uk/swbio/apply/eligibility.html


Funding Notes

Funding: The studentship will cover a stipend (currently £14,057pa), research costs and tuition fees at the UK/EU rate for students who meet the residency requirements outlined by the BBSRC. Students from EU countries who do not meet the residency requirements may still be eligible for a fees-only award.

References

Brunt LH, Norton JL, Bright JA, Rayfield EJ, Hammond CL. 2015. Finite element modelling predicts changes in joint shape and cell behaviour due to loss of muscle strain in jaw development. J Biomech. 48(12):3112-22

Zancan I, Bellesso S, Costa R, Salvalaio M, Stroppiano M, Hammond C, Argenton F, Filocamo M, Moro E. 2015. Glucocerebrosidase deficiency in zebrafish affects primary bone ossification through increased oxidative stress and reduced Wnt/β-catenin signaling. Hum Mol Genet. 24(5):1280-94
Hayes AJ, Reynolds S, Nowell MA, Meakin LB, Habicher J, Ledin J, Bashford A, Caterson B,Hammond CL. 2013. Spinal deformity in aged zebrafish is accompanied by degenerative changes to their vertebrae that resemble osteoarthritis. PLoS One. 8(9):e75787

Robson Brown K, Tarsuslugil S, Wijayathunga VN, Wilcox RK. 2014. Comparative finite-element analysis: a single computational modelling method can estimate the mechanical properties of porcine and human vertebrae. J R Soc Interface.;11(95):20140186.

Hammond CL, Moro E. 2012. Using transgenic reporters to visualize bone and cartilage signaling during development in vivo.Front Endocrinol.;3:91.

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