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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
- 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?
- 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
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11. Understanding the mechanisms of insulin secretion in patients with HADH mutations
Supervisor Pair: Dr Khalid Hussain and Dr Simon Eaton
Potential Student’s Home Department: Clinical and Molecular Genetics Unit, Institute of Child Health
Pancreatic beta-cells secrete insulin in response to glucose, amino acids and fatty acids. Glucose metabolism is the key for glucose induced insulin secretion and amino acids (such as leucine) control insulin secretion by regulating the activity of the enzyme glutamate dehydrogenase. The mechanism/s of how fatty acids control insulin secretion is unclear. Our preliminary clinical and biochemical data have shown that the enzyme Short Chain 3-Hydroxy-Acyl-CoA Dehydrogenase (HADH) plays a key role in regulating both fatty acid and amino acid induced insulin secretion. We have identified patients with HADH mutations that have defects in fatty acid and amino acid induced insulin secretion. However the molecular mechanisms of how HADH mutations lead to abnormalities in insulin secretion are still unclear. This project will focus on trying to unravel the genetic and biochemical basis of insulin secretion in patients with defects in HADH.
This project addresses human wellbeing. Our clinical observations on patients with HADH mutations have provided fundamental new insights into how insulin secretion is regulated by fatty acid and amino acid metabolism. We have shown for the first time that a defect in fatty acid oxidation (HADH deficiency) makes patients hypersensitive to the amino acid leucine (JCEM 2010, Orphanet J Rare Dis 2012). These clinical observations have important implications for patient management (preventing hypoglycaemia by restricting protein in the diet) and have unravelled a new biochemical pathway involved in regulating insulin secretion by fatty acid oxidation and amino acid metabolism.