PhD studentship 2010
Analysis of changes in gastrointestinal appetite
hormones and hypothalamic circuitry during pregnancy and
lactation, funded by the Open University.
Title:
Supervisory team: Dr Vicky Taylor and Dr Jill Saffrey,
Department of Life Sciences, Open University, Milton Keynes, Buckinghamshire MK7 6AA, UK.
Background
Pregnancy and lactation are characterised by altered hormone secretion and metabolic
changes. These neuroendocrine adjustments result in increased appetite and altered feeding
behaviour that orchestrate the mother’s adaptation to these metabolically demanding
conditions. Known adaptations include changes in orexigenic (appetite-stimulating) and
anorexigenic (appetite-suppressing) signals produced in (i) the brain, i.e. hypothalamus, such
as neuropeptide Y (NPY), agouti-related protein (AgRP) and alpha-melanocortin-stimulating
hormone (a-MSH) and (ii) the periphery, e.g. metabolites and hormones, such as leptin from
adipose tissue. Additionally, the gastrointestinal tract secretes hormones, including the appetiteregulators ghrelin and peptide YY (PYY) and during pregnancy and lactation the gut increases
in both mass and surface area. Thus pregnancy and lactation are intriguing natural states in
which to study the role of gastrointestinal and other hormones implicated in the control of
appetite, changing gut architecture and whole body homeostasis. The wider implications of this
research area include pregnancy as a time of retained weight gain in humans, which has future
health implications for the mother but also has effects on offspring in utero that may influence
their future metabolic responses to modern obesogenic environments.
Our previous work in this area investigated the plasma and tissue profiles of the gastrointestinal
hormones ghrelin and peptide YY (PYY) in different female rat reproductive states (Taylor et al.,
2009). Ghrelin was unsuppressed during pregnancy despite elevated leptin concentrations.
PYY steadily increased throughout pregnancy and lactation. Relative PYY concentrations in the
tissues of the gut varied in the different physiological states suggesting regional alterations
taking place in the colon. Why PYY, an endogenous satiety factor, was found to be consistently
raised in various tissues during pregnancy, when it was expected to be decreased to facilitate
energy intake, remains to be established. Pregnancy has already been associated with insulin
and leptin-resistance and these data raise the possibility that it may also be resistant to the
effects of some appetite hormones. Thus PYY may have an influence on maternal dietary
adaptation, intestinal hypertrophy and weight gain during pregnancy and lactation although it is
still unclear precisely how it acts.
This studentship will build on these previous observations, exploring their endocrine and
physiological background in more detail during different reproductive states along with structural
changes in the gastrointestinal tract. The distribution patterns and mechanisms of action of gut
hormones and brain neuropeptide gene expression will be examined under various
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experimentally manipulated conditions (quality and amount of diet/physical activity; parity; litter
size; etc), and effects on offspring physiology/endocrinology will also be explored. The work will
include some of the following wide range of analytical techniques:
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Exploring
changes
in
gastrointestinal
ghrelin/PYY-secreting
cells
using
immunohistochemistry (IHC) and electron microscopy (EM);
Monitoring and measuring physical variables i.e. feeding behaviour, body and organ
changes;
Measuring cell proliferation using cell culture of primary cells and proliferation assays;
Investigating mRNA and gene expression of peptides, hormone receptors,
neuropeptides from a range of tissues using in situ hybridisation (ISH) and RTpolymerase chain reaction (RT-PCR);
Measuring circulating hormones and metabolites using enzyme-linked immunosorbent
assays (ELISA), radioimmunoassays (RIA), liquid chromatography mass spectrometry
(LCMS);
Measuring cytokines and fatty acid profiles in adipose depots using ELISA and gas
chromatography (GC).
The work will focus on laboratory rodents but there may also be opportunities to analyse blood
samples from pregnant and lactating women.
Studentship
The Studentship provides a stipend of at least £13,290 per year for 3 years plus tuition fees with
an anticipated start date of 1 October 2010. The work will be full-time in the newly refurbished
laboratories at the Open University, Milton Keynes, and the student will need to be conveniently
placed to travel to the University. There may also be local travel to Milton Keynes General
Hospital to collect blood samples. This kind of work may require working outside the standard
working day/week and therefore all applicants should consider the feasibility of this before
applying.
The PhD student would be fully engaged in the OU PhD training programme and would be
engaged for 3 years with submission of the thesis expected within that timeframe. The student
will participate in the OU Life Sciences departmental programme of seminars and journal clubs
as well as short courses in research writing, research ethics, safety, etc.
References and further information:
Taylor VJ, Patterson M, Ghatei MA, Bloom SB Wilson CA (2009) Ghrelin and peptide YY (PYY)
profiles in gastrointestinal tissues and the circulation of the rat during pregnancy and lactation.
Peptides 30: 2213-20.
Taylor VJ, Jethwa P, Small CJ, Bloom SB (2004) Gut hormones and the regulation of appetite.
Trends in Pharmacological Sciences: 25, Issue 10
Many OU research articles are available via Open Research Online (ORO):
http://oro.open.ac.uk/view/person/vjt63.html
Life Sciences Dept website: http://www.open.ac.uk/science/lifesciences/research/research.php?
OU PhD training programme: http://www.open.ac.uk/research/research-degrees/overview.php?
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