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Dr A W Simpson
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
Options within Ca2+ signalling.
Ca2+ signalling in skin: A gradient of intracellular and extracellular Ca2+ exists across the epidermis. It is essential for the normal control of proliferation and differentiation of keratinocytes. Loss and subsequent restoration of this gradient is a part of the wound repair process. However, disruption of the gradient also occurs in psoriasis and other skin disorders such as Darier and Hailey Hailey. This project will examine how the gradient is generated in healthy, healing and diseased conditions with a view to enhancing the healing process.(1, 2)
Regulation of Ca2+ efflux in hepatocytes: Toxic and hypoxic stress leads to a cytotoxic elevation of Ca2+ in hepatocytes. Activation of Ca2+ efflux by elevation of cGMP is cytoprotective. Little is known about how elevated cGMP activates the plasma membrane Ca2+ ATPase (PMCA) responsible for Ca2+ efflux. This project will examine the molecular mechanisms involved in cGMP mediated regulation of the PMCA(3, 4).
Mitochondria and memory: Mitochondria influence many aspects of neuronal function. In particular, mitochondrial proteins such as MAOA and TOMM40 are associated with behaviour, cognitive function, IQ and various neurological disorders including Alzheimer’s (5, 6). As well as generating ATP, mitochondria influence the formation of Ca2+ signals within neurones(1, 7) . The link between mitochondrial protein variants and cognitive ability warrants further investigation (8). In this study we shall examine how specific protein variants, identified by GWAS and candidate gene studies to affect CNS function, impact on mitochondrial function.
Ca2+ signalling in skin: A gradient of intracellular and extracellular Ca2+ exists across the epidermis. It is essential for the normal control of proliferation and differentiation of keratinocytes. Loss and subsequent restoration of this gradient is a part of the wound repair process. However, disruption of the gradient also occurs in psoriasis and other skin disorders such as Darier and Hailey Hailey. This project will examine how the gradient is generated in healthy, healing and diseased conditions with a view to enhancing the healing process.(1, 2)
Regulation of Ca2+ efflux in hepatocytes: Toxic and hypoxic stress leads to a cytotoxic elevation of Ca2+ in hepatocytes. Activation of Ca2+ efflux by elevation of cGMP is cytoprotective. Little is known about how elevated cGMP activates the plasma membrane Ca2+ ATPase (PMCA) responsible for Ca2+ efflux. This project will examine the molecular mechanisms involved in cGMP mediated regulation of the PMCA(3, 4).
Mitochondria and memory: Mitochondria influence many aspects of neuronal function. In particular, mitochondrial proteins such as MAOA and TOMM40 are associated with behaviour, cognitive function, IQ and various neurological disorders including Alzheimer’s (5, 6). As well as generating ATP, mitochondria influence the formation of Ca2+ signals within neurones(1, 7) . The link between mitochondrial protein variants and cognitive ability warrants further investigation (8). In this study we shall examine how specific protein variants, identified by GWAS and candidate gene studies to affect CNS function, impact on mitochondrial function.
References
1. Laude AJ, Simpson AWM. Compartmentalized signalling: Ca(2+) compartments, microdomains and the many facets of Ca(2+) signalling. Febs J. 2009;276(7):1800-16.
2. Savignac M, Edir A, Simon M, Hovnanian A. Darier disease : a disease model of impaired calcium homeostasis in the skin. Biochimica et biophysica acta. 2011;1813(5):1111-7. Epub 2010/12/21.
3. Green AK, Stratton RC, Squires PE, Simpson AWM. Atrial natriuretic peptide attenuates elevations in Ca(2+) and protects hepatocytes by stimulating net plasma membrane Ca(2+) efflux. J Biol Chem. 2007;282(47):34542-54.
4. Green AK, Zolle O, Simpson AWM. Atrial natriuretic peptide attenuates Ca2+ oscillations and modulates plasma membrane Ca2+ fluxes in rat hepatocytes. Gastroenterology. 2002;123(4):1291-303.
5. Ferrer I. Early involvement of the cerebral cortex in Parkinson's disease: convergence of multiple metabolic defects. Progress in neurobiology. 2009;88(2):89-103. Epub 2009/06/02.
6. Ben-Shachar D. The interplay between mitochondrial complex I, dopamine and Sp1 in schizophrenia. J Neural Transm. 2009;116(11):1383-96. Epub 2009/09/29.
7. Contreras L, Drago I, Zampese E, Pozzan T. Mitochondria: the calcium connection. Biochimica et biophysica acta. 2010;1797(6-7):607-18. Epub 2010/05/18.
8. Byrne EM, McRae AF, Duffy DL, Zhao ZZ, Martin NG, Wright MJ, et al. Association study of common mitochondrial variants and cognitive ability. Behavior genetics. 2009;39(5):504-12. Epub 2009/05/19.
2. Savignac M, Edir A, Simon M, Hovnanian A. Darier disease : a disease model of impaired calcium homeostasis in the skin. Biochimica et biophysica acta. 2011;1813(5):1111-7. Epub 2010/12/21.
3. Green AK, Stratton RC, Squires PE, Simpson AWM. Atrial natriuretic peptide attenuates elevations in Ca(2+) and protects hepatocytes by stimulating net plasma membrane Ca(2+) efflux. J Biol Chem. 2007;282(47):34542-54.
4. Green AK, Zolle O, Simpson AWM. Atrial natriuretic peptide attenuates Ca2+ oscillations and modulates plasma membrane Ca2+ fluxes in rat hepatocytes. Gastroenterology. 2002;123(4):1291-303.
5. Ferrer I. Early involvement of the cerebral cortex in Parkinson's disease: convergence of multiple metabolic defects. Progress in neurobiology. 2009;88(2):89-103. Epub 2009/06/02.
6. Ben-Shachar D. The interplay between mitochondrial complex I, dopamine and Sp1 in schizophrenia. J Neural Transm. 2009;116(11):1383-96. Epub 2009/09/29.
7. Contreras L, Drago I, Zampese E, Pozzan T. Mitochondria: the calcium connection. Biochimica et biophysica acta. 2010;1797(6-7):607-18. Epub 2010/05/18.
8. Byrne EM, McRae AF, Duffy DL, Zhao ZZ, Martin NG, Wright MJ, et al. Association study of common mitochondrial variants and cognitive ability. Behavior genetics. 2009;39(5):504-12. Epub 2009/05/19.
Project supervisors
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