The aim of the study proposed in this fellowship is to investigate an important brain system implicated in depression, the hypothalamic pituitary adrenal (HPA) axis, using a mouse model of social support. Stress plays an important role in the development o f depression and stressful life events have often been associated with the onset of depression. Social support has been found to have a positive effect on the outcome of a depressive episode, and may be acting as a buffer to protect against stress-related disorders. There is growing evidence for gender differences in response to such support that may be a reflection of the different coping strategies employed by men compared with women in response to stress. Functional genomic techniques in mouse offer a uniquely integrative approach in the analysis of the biology of a system in response to an environmental manipulation such as stress, leading to the identification of both gene-gene and gene-environment interactions.
A multi-factorial set of studies are proposed that will investigate the interplay of gender, environment and genes at the level of behaviour, HPA axis physiology and gene expression using a powerful genetic tool, a panel of chromosome substitution strains (CSS) of mice generated from A/J (donor) and C57BL/6J (host) inbred strains of mice. The fellowship will provide training in physiological monitoring using telemetry and vena jugularis cannulation, using a novel and highly innovative approach of integrating data from different processes across a complex system. The fellow will gain invaluable training experience from researchers who excel in the field of physiological recording and the skills in systems biology gained will be of considerable benefit in developing an independent research career.
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