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Our strategy is to adopt a life course approach towards an understanding of the aetiology and underlying mechanisms of common metabolic, cardiovascular and neurological disorders from reproductive dysfunction, fetal and neonatal development through initiation and progression to adult disease.
Research spans the characterisation of nutritional and environmental influences on mammalian reproductive function as well as the long-term consequences of such stimuli for neurodevelopment, physiological dysfunction and subsequent risk of disease. This includes the investigation of the nutritional and hormonal influences on central regulatory pathways of the ovulatory cycle, including the elucidation of molecular components of the central 24 hr (circadian) clock and their response to ageing, the role of melatonin in circadian and homeostatic sleep mechanisms and the neural mechanisms of stress-induced dysfunction of reproductive neuroendocrine functions.
The interaction of genes and the early life environment is a central focus with particular reference to the impact of nutrition and metabolic states on both pregnancy outcome and early life origins of disease; this spans from investigation of oocyte development and function to the underlying mechanisms of adult metabolic and cardiovascular disease. Furthermore, research into reproductive and neurodevelopmental aspects of psychiatry is developing our understanding of the interactions between stress, sex hormones and gender on neurodevelopment from fetus to old age.
The group fosters translation between basic and clinical research and has key links with the Menopause Research, Reproductive Medicine and Fetal and Infant Health RDUs. Within the RDU, there are the following research themes:
Reproductive Neurobiology & Early Life Origins of Disease
DESCRIPTION
This research grouping, led by Professor Lucilla Poston, Professor Clive Coen, Professor Kevin O'Byrne, Dr Paul Taylor and Dr David Sugden, brings together both basic science and clinical research expertise in cellular and reproductive endocrinology, developmental biology, neuroanatomy, and neurodevelopmental psychiatry with the overarching themes of developmental programming or the early life origins of disease and healthy ageing.Our strategy is to adopt a life course approach towards an understanding of the aetiology and underlying mechanisms of common metabolic, cardiovascular and neurological disorders from reproductive dysfunction, fetal and neonatal development through initiation and progression to adult disease.
Research spans the characterisation of nutritional and environmental influences on mammalian reproductive function as well as the long-term consequences of such stimuli for neurodevelopment, physiological dysfunction and subsequent risk of disease. This includes the investigation of the nutritional and hormonal influences on central regulatory pathways of the ovulatory cycle, including the elucidation of molecular components of the central 24 hr (circadian) clock and their response to ageing, the role of melatonin in circadian and homeostatic sleep mechanisms and the neural mechanisms of stress-induced dysfunction of reproductive neuroendocrine functions.
The interaction of genes and the early life environment is a central focus with particular reference to the impact of nutrition and metabolic states on both pregnancy outcome and early life origins of disease; this spans from investigation of oocyte development and function to the underlying mechanisms of adult metabolic and cardiovascular disease. Furthermore, research into reproductive and neurodevelopmental aspects of psychiatry is developing our understanding of the interactions between stress, sex hormones and gender on neurodevelopment from fetus to old age.
The group fosters translation between basic and clinical research and has key links with the Menopause Research, Reproductive Medicine and Fetal and Infant Health RDUs. Within the RDU, there are the following research themes:
- Developmental Programming of Adult Disease
- Reproductive function nutritional and environmental influences
- Reproductive and Neurodevelopmental Psychiatry.
Associated research programmes
Associated staff research interests
Interests:
Integrative neuroscience, neurobiology of reproduction and sociality, nutritional influences on reproductive physiology, early life programming for obesity, Circadian biology.
Tel:
020 7848 6205
Fax:
020 7848 6280
Email:
Website:
Interests:
Melatonin: The pineal hormone, melatonin shows a dramatic, precisely-regulated circadian rhythm of synthesis and release. It acts through specific, high affinity, G-protein-coupled cell membrane receptors to regulate circadian and seasonal physiological changes. We are involved in a collaborations with chemists at University College London and the University of Athens to design, synthesize and evaluate novel melatonin analogs. The project aims to understand the molecular basis of the recognition of melatonin, receptor activation and subtype specificity. We have developed some of the first subtype selective melatonin receptor agonists and antagonists. Novel analogues are examined in vitro, and in cell systems. In addition, in vivo effects on circadian rhythms in activity, temperature and sleep are monitored by telemetry. We are currently investigating the role of endogenous melatonin in sleep, and the mechanism of action of exogenous melatonin as a hypnotic. Melatonin analogs have recently been licensed for sleep problems and depression. Chronic sleep disturbance (often caused by desynchronised circadian rhythms) is increasingly recognised as an important risk factor for cardiovascular disease and metabolic disorders. We are interested in the effects of circadian disruption on health and have substantial experience of using radiotelemetry in small animals for chronic measurement of physiology and behaviour.
Quantitation of gene expression: Over several years the group has built expertise and state-of-the-art facilities for gene expression analysis using qPCR and has played a major role in spreading best practice in this technique in the UK through a variety of training courses attracting participants from the UK, Europe, South America and the Middle East. I am involved with a number of projects using real-time RT-PCR to quantitate steady-state levels of gene expression in various endocrine and neural cells and tissues. One of these projects in collaboration with Dr David Klein (NIH, USA) is a detailed examination of the circadian control of the expression of the genes encoding proteins (receptors, enzymes, transcription factors etc.) known to be important for the nocturnal synthesis of melatonin. Others include studies using qPCR assays to validate microarray data..
Melanopsin: Melanopsin is a novel, retinal, opsin-like protein, first identified in skin cells (melanophores) of Xenopus leavis. Recent work shows that it acts as light detector mediating the entraining action of light on the circadian clock in the SCN, and various other effects of light. We are using a Xenopus melanophore cell line, which naturally expresses melanopsin and also responds to light with a dramatic redistribution of pigment granules, as a model system to study melanopsin photo-biology, signal transduction mechanisms and function.
Quantitation of gene expression: Over several years the group has built expertise and state-of-the-art facilities for gene expression analysis using qPCR and has played a major role in spreading best practice in this technique in the UK through a variety of training courses attracting participants from the UK, Europe, South America and the Middle East. I am involved with a number of projects using real-time RT-PCR to quantitate steady-state levels of gene expression in various endocrine and neural cells and tissues. One of these projects in collaboration with Dr David Klein (NIH, USA) is a detailed examination of the circadian control of the expression of the genes encoding proteins (receptors, enzymes, transcription factors etc.) known to be important for the nocturnal synthesis of melatonin. Others include studies using qPCR assays to validate microarray data..
Melanopsin: Melanopsin is a novel, retinal, opsin-like protein, first identified in skin cells (melanophores) of Xenopus leavis. Recent work shows that it acts as light detector mediating the entraining action of light on the circadian clock in the SCN, and various other effects of light. We are using a Xenopus melanophore cell line, which naturally expresses melanopsin and also responds to light with a dramatic redistribution of pigment granules, as a model system to study melanopsin photo-biology, signal transduction mechanisms and function.
Tel:
020 7848 6274
Fax:
020 7848 6280
Email:
Website:
Interests:
stress and infertility, early life programming and puberty, hot flushes
Tel:
020 7848 6286
Fax:
020 7848 6220
Email:
kevin.o'byrne@kcl.ac.uk
Website:
Interests:
The scientific community is increasingly aware that susceptibility to disease may originate in the earliest stages of human life. Population studies world-wide have shown that individuals who are undernourished in utero are more susceptible to cardiovascular and metabolic disease in later life.
Research from Professor David Barker’s unit at Southampton University over the last 20 years has sparked a remarkable resurgence in interest into the physiology of fetal nutrition. Working in collaboration with the Southampton Unit and colleagues at Cambridge and Nottingham universities, our Unit has developed several rodent models to probe the mechanisms underlylng the developmental origins of adulthood disease. Our focus has not been on undernutrition, but on overnutrition as we have shown that a maternal diet rich in fat and calories can also lead to development of disease in the offspring. We have shown that rats and mice exposed in utero to a diet rich in fat and simple sugars develop hypertension, insulin resistance and obesity.
The observation that maternal obesity and a hypercalorific diet in rodents can ‘programme’ obesity in the developing child has generated considerable interest, not to mention concern, should it be proven that this also occurs in human pregnancy. Indeed, some observational studies from other groups working with women and their children have provided some evidence to support a similar transmission of an obesogenic trait from mother to baby.
We are now pursuing our animal models with a view to understanding the underlying mechanisms, with particular focus on the hypothesis that the maternal nutritional environment may permanently ‘rewire’ the appetite control centres of the developing hypothalamus. Unravelling the epigenetic mechanisms which ensure persistent alteration of physiological and biochemical function from the in utero and early post natal environment, through to adult life presents a terrific challenge Some insight has been gained from recent work in our group which has suggested that the mitochondrion may carry the ‘memory’ and be causative in the later development of disease.
In pregnant women we are carrying out an NIHR funded intervention study to improve pregnancy outcome . Having developed and piloted a physical activity and dietary intervention we shall carry out a large national randomised study. As well as improving pregnancy outcome we anticipate that this study will provide valuable information in regard to the developmetal origins of obesity.
Research from Professor David Barker’s unit at Southampton University over the last 20 years has sparked a remarkable resurgence in interest into the physiology of fetal nutrition. Working in collaboration with the Southampton Unit and colleagues at Cambridge and Nottingham universities, our Unit has developed several rodent models to probe the mechanisms underlylng the developmental origins of adulthood disease. Our focus has not been on undernutrition, but on overnutrition as we have shown that a maternal diet rich in fat and calories can also lead to development of disease in the offspring. We have shown that rats and mice exposed in utero to a diet rich in fat and simple sugars develop hypertension, insulin resistance and obesity.
The observation that maternal obesity and a hypercalorific diet in rodents can ‘programme’ obesity in the developing child has generated considerable interest, not to mention concern, should it be proven that this also occurs in human pregnancy. Indeed, some observational studies from other groups working with women and their children have provided some evidence to support a similar transmission of an obesogenic trait from mother to baby.
We are now pursuing our animal models with a view to understanding the underlying mechanisms, with particular focus on the hypothesis that the maternal nutritional environment may permanently ‘rewire’ the appetite control centres of the developing hypothalamus. Unravelling the epigenetic mechanisms which ensure persistent alteration of physiological and biochemical function from the in utero and early post natal environment, through to adult life presents a terrific challenge Some insight has been gained from recent work in our group which has suggested that the mitochondrion may carry the ‘memory’ and be causative in the later development of disease.
In pregnant women we are carrying out an NIHR funded intervention study to improve pregnancy outcome . Having developed and piloted a physical activity and dietary intervention we shall carry out a large national randomised study. As well as improving pregnancy outcome we anticipate that this study will provide valuable information in regard to the developmetal origins of obesity.
Tel:
020 7188 3639
Fax:
020 7620 1227
Email:
Website:
Interests:
Dr Taylor’s research interests include the ‘developmental programming’ effects of maternal nutrition and the hormonal environment in pregnancy on the offspring’s future cardiovascular and metabolic development. The goal of the Developmental Programming Research Group is “To understand the consequences of maternal obesity and poor nutrition in pregnancy on the future health of the child”. Specifically, the group aim to investigate the physiological processes and the cellular and molecular mechanisms whereby a baby’s exposure to an aberrant hormonal or nutritional environment in pregnancy and lactation gives rise to increased risk of obesity and associated disorders in later life. These include the ‘metabolic syndrome’, a triad of diabetes, high blood pressure and raised cholesterol in the blood. Dr Taylor has previously been the recipient of a British Heart Foundation Junior Research Fellowship and has been awarded 5 project grants in the last 5 years (3 as principal investigator) within the field of Developmental Programming. Recent publications include a recent review for Experimental Physiology on the Developmental Programming of Obesity and several related book chapters. Original articles include publications the Journal of Hypertension and the Journal of Physiology investigating the effect of maternal high fat diet in pregnancy on offspring phenotype and a recent Circulation paper provided proof of concept for the Predictive Adaptive Responses hypothesis.
Tel:
020 7188 3630
Fax:
020 7620 1227
Email:
Website:
CONTACTS FOR FURTHER INFORMATION
Hannah Powles
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