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- 1. Bayesian Modelling of Disease Progression In juvenile dermatomyositis (JDM)
- 2. Mind-body interactions influencing the outcome of treatment for epilepsy
- 3. Treating retinal inflammation: bridging the divide between common problems in the eye and the brain
- 4. Development of a Novel In Vivo Animal Model for Schizophrenia Drug Testing
- 5. Immune mechanisms in Developmental Programming of Non-Alchoholic Fatty Liver Disease
- 8. Using social media big data to understand the genetic and environmental aetiology of mental health and disorder in emerging adulthood
- 10. Molecular Control of Pain Processing
- 11. Understanding the mechanisms of insulin secretion in patients with HADH mutations
- 12. Origins of cortico-subthalamic “hyperdirect” pathway in the motor cortex: electrophysiology and imaging
- 13. The mechanical control of tissue regeneration.
- 14. Investigating community severance in Southend and its effects on health and access to healthcare
- 15. Ageing of the liver and protection from injury: from flies to mice to humans
- 16. Intelligent nanomaterials against antibiotic resistant bacteria
- 17. Retroviral restriction factors that control species-specific gene regulation and stem cell fate
- 18. Improving women’s choice and uptake of effective contraceptive methods through development of interactive digital interventions
- 19. From embryonic cell to neuron: understanding the complexity of developmental decisions
- 20. Identification of mitochondrial biomarkers and therapeutic targets in pancreatic cancer
- 23. Television subtitling for deaf and hearing-impaired viewers: a route to improve English language skills for UK migrants with normal hearing
- 24. Large-scale phylogenomic mapping of domain architecture changes to elucidate gene function evolution
- 25. Calcium channel trafficking, nociceptive neurotransmission and mechanism of action of gabapentinoid drugs in mouse models of neuropathic pain
- 26. Real-time and nanometre-scale visualisation of membrane perforation in pathogen attack and immune response
- 22. Understanding the molecular mechanisms of pancreatic cancer progression
- 27. Forming a sensory map: the role of auditory and visual cues in the hippocampal representation of space
- 29. Human amniotic fluid-derived induced pluripotent stem cells for the treatment of osteogenesis imperfecta.
- 31. Understanding the immunopathogenesis of juvenile-onset SLE: could targeting lipid biosynthesis control disease progression and reduce cardiovascular risk?
- 30. Shared Control Wheelchair Interfaces
- 32. Understanding the neurobiological effects of clinical photochemical internalisation in order to minimise nerve damage during treatment of cancer
- 33. Shedding light on the ethnic attainment gap: The influence of intercultural relations on students’ learning and performance
- 34. Patient-focused development of a versatile, wearable neurostimulation device to control urinary incontinence.
- 35. The development and evaluation of positive psychology outcome measures for people with dementia
- 36. Rehabilitation strategies to improve balance and prevent falls in people with Charcot-Marie-Tooth disease
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Supervisor Pair: Dr Christophe Dessimoz and Professor Christine Orengo
Potential Student’s Home Department: Genetics, Evolution and Environment
A powerful way of characterising newly sequenced genes is to compare them with evolutionarily related genes. Gene-centric phylogenomic databases such as OMA, developed in the primary supervisor’s lab, elucidate the evolutionary history of proteins in terms of two key evolutionary processes: speciation events (which yield orthologous genes) and duplications events (which yield paralogous genes). However, by focusing on proteins in their full-length, these databases and associated methods largely ignore domain architecture changes (such as gene fusion, fission, domain shuffling, etc.), thus failing to account for a major source of protein function innovation and adaptation.
In this project, we will develop a new method to systematically identify domain architecture changes and infer where they occurred in terms of the evolutionary histories of the gene families involved. In this way, new links reflecting architecture changes will be established between as-of-yet disconnected orthologous groups. In turn, this will pave the route to improvements in protein function propagation and will provide a more comprehensive and integrated framework to study protein evolution across thousands of species.
Understanding how new domain architectures evolve and modify the functions of the proteins will be extremely valuable in function prediction protocols. Since for most organisms, even human, fewer than 10% of genes have detailed experimental characterisation understanding how protein function diverges will benefit prediction algorithms. The Orengo group have expertise in function prediction methods and were ranked 7th (out of 56 methods) in a recent international assessment (CAFA) of prediction methods (Nature Methods, 2013).
The project builds upon the considerable relevant experience and infrastructure of the supervising team, including the OMA orthology database and the CATH protein domain database—two leading resources in their respective areas.