Since moving to the UK from Singapore in 1996, my research group has established a fully multi-disciplinary approach to understand the role of the central nervous system in homeostatic regulation. This has been most successful and informative, with over 140 primary research papers published in high impact peer-reviewed international journals, and many invitations to both national and international meetings. I have also been very active in the organisation of international conferences, including, in 2013, the 10th World Congress of Neurohypophyseal Hormones held in Bristol. International honours have included an Honorary Professorship at the University of the North (South Africa; now the University of Limpopo) and Visiting Professorships at the University of Belgrade (Serbia) and the University of Malaya (Malaysia). I am very active in the reviewing process for research grants and papers, both at national and international level. I am an editor for The American Journal of Physiology – Regulatory, Integrative and Comparative Physiology (The American Physiological Society) and for Frontiers in Molecular Neuroscience. I am a member of the BBSRC Pool of Experts. I have brought lots of research money to the University (including 3 programme grants); over the past 7 years, I have generated ~£7.5 million in grant income. Since joining the University of Bristol in 1996, I have contributed to the generation of ~£20 million in grant income. Of this, I personally raised over ~£10 million as principal investigator.

 

Research highlights over the past 10 years have included:

• The use of transgenic rats and models to show that autophagy, a bulk process that delivers regions of cytosol to lysosomes for degradation, is implicated in the aetiology of Familial Neurohypophyseal Diabetes Insipidus (FNDI), an autosomal dominant progressive neurodegenerative disorder of arginine vasopressin (VP) neurons that presents as excessive drinking and urination as a consequence of a loss of VP secretion from posterior pituitary nerve terminals.

• The development of novel germline transgenic rats that enable VP neurons to be identified by virtue of their expressing enhanced green fluorescent protein (eGFP). Using fluorescence detection, VP gene expression and VP release can be readily monitored in live cells in real-time.

• The development of novel viral vectors as specific tools to disentangle neuronal mechanisms and image specific cell phenotypes in the brain.

• The dissection of the molecular events that take place in VP neurons following the onset of a dehydration stimulus. For example, we have used germline transgenic rats to map the genomic sequences responsible for the cell-specific and physiological expression of the VP gene in the hypothalamus, and shown that inhibition of specific signaling systems within VP neurons using viral vector mediated gene transfer can reduce dehydration-induced gene expression.

• The use of microarrays and, latterly, RNAseq to describe global changes in gene expression in brainstem, hypothalamic and circumventricular brain regions following physiological (dehydration, starvation) and pathological (hypertension, chronic heart failure) disturbance.

• Functional investigations on novel genes identified by transcriptomics. Thus, we have amply demonstrated the value of transcriptomic approaches in delivering novel physiological understanding by identifying novel genes involved in the biosynthesis of VP (Creb3l1, Azin1, Caprin-2), the physiological response of VP neurones to osmotic cues (Slc12a1), and the behavioural control of water and salt ingestion (Giot1, Rasd1). A coherent and essential component of this research strategy is the training of future generations of scientists.