<ns2:projects xmlns:ns1="http://gtr.rcuk.ac.uk/gtr/api"
              xmlns:ns2="http://gtr.rcuk.ac.uk/gtr/api/project"
              xmlns:ns3="http://gtr.rcuk.ac.uk/gtr/api/project/outcome"
              xmlns:ns4="http://gtr.rcuk.ac.uk/gtr/api/organisation"
              xmlns:ns5="http://gtr.rcuk.ac.uk/gtr/api/person" xmlns:ns6="http://gtr.rcuk.ac.uk/gtr/api/fund"
              ns1:page="1" ns1:size="20" ns1:totalPages="3417" ns1:totalSize="68323">
	<ns2:project ns1:id="E178742B-571B-498F-8402-122F17C47546"
	             ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/projects/E178742B-571B-498F-8402-122F17C47546"
	             ns1:created="2016-11-11T20:42:55Z">
		<ns1:links test="ciao">
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/persons/CB8C3733-D17E-46A8-9E7C-D5A76F36612A"
					ns1:rel="PI_PER"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/persons/95D46800-A4DF-40AC-8FD3-7EAF5194B22C"
					ns1:rel="COI_PER"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/organisations/8319F78A-DCBD-49F6-BE00-78E1CD75CDA9"
					ns1:rel="LEAD_ORG"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/funds/B794CB74-BD85-452B-8030-69BD4AF82CE9"
					ns1:rel="FUND" ns1:start="2007-06-01T00:00:00+01:00"
					ns1:end="2010-05-31T00:00:00+01:00"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/outcomes/publications/2A19F274-8BAF-4AFC-865C-638BFB5FBDB9"
					ns1:rel="PUBLICATION"/>
		</ns1:links>
		<ns2:identifiers>
			<ns2:identifier ns2:type="RCUK">BB/E021409/1</ns2:identifier>
		</ns2:identifiers>
		<ns2:title> A multicellular 3D stem cell model to define the role of stroma in epithelial
			differentiation </ns2:title>
		<ns2:status>Closed</ns2:status>
		<ns2:grantCategory>Research Grant</ns2:grantCategory>
		<ns2:leadOrganisationDepartment>Biology</ns2:leadOrganisationDepartment>
		<ns2:abstractText> In aging men the disorders of prostate are a major medical problem.
			Benign prostatic hyperplasia and cancer are increasingly prevalent. To find cures for
			these diseases it is essential to understand how the prostate grows and functions
			normally. All organs have their own population of stem cells which grow and develop into
			a variety of cells which communicate to form correct organ architecture and function.
			This occurs as a result of signals from the stem cell's own genes but also from signals
			provided by neighbouring cells, known as stroma. In the prostate, how this occurs is
			unknown. We propose to develop a model to grow gland-like structures from adult stem
			cells in the laboratory. The model will be employed to understand how stromal cells
			influence prostate cellular architecture. We aim to identify proteins which act as
			signals from the stroma to change epithelial shape. The shape of a cell has important
			effects on cell function. These experiments will increase our knowledge of how tissues
			develop and function. Development of tissue-like models based on human cells will
			provide a valuable gap between results from animal models and human clinical studies, to
			help understand the basic mechanisms of human physiology and disease. Such model systems
			will reduce the need for animal experimentation, which is currently the best way to
			investigate complex cell interactions in tissues. We anticipate the model will aid
			university directed research into human differentiation and disease mechanisms, but also
			for the pharmaceutical industry to screen new drugs for efficacy and safety in humans
			before trial. </ns2:abstractText>
		<ns2:techAbstractText> Recent advances in our lab have resulted in the isolation of human
			adult prostate stem cells and the development of 3D models of prostatic acini from basal
			cells. Results from 3D modelling indicate that stroma is important for epithelial
			morphogenesis and differentiation. Importantly, stromal cultures increase epithelial
			cell polarity and columnar cell shape. Using electron microscopy and RT-PCR our
			preliminary data has found that these morphological effects are accompanied by increased
			desmosomal expression. We now wish to develop our tissue engineering to produce a 3D
			model of prostatic acini using a homogeneous population of stem cells. A stem cell model
			will allow the study of full epithelial differentiation and the stem cell niche. It is
			important to model the prostate with human cells because the mouse prostate has a
			different anatomy, cell structure and protein function, and does not develop equivalent
			diseases to humans. The model will be used to investigate our hypothesis that 'stroma
			signals to control epithelial cell shape and polarity'. We will confirm which desmosomal
			isoforms are present in prostate epithelial acini and which are upregulated by stromal
			cultures, using Western Blotting and real time PCR. Upregulated desmosomal isoforms will
			be used as markers for epithelial cell polarity and shape. A differential gene
			expression profile will be generated from stroma grown with epithelial acini in 3D
			culture and stroma grown in 3D culture without acini, using microarray analysis.
			Candidate stromal genes will be identified that signal to upregulate epithelial polarity
			(desmosomal expression) and their function will be confirmed using siRNA knockdown
			studies. This is a novel pathway for epithelial cell differentiation which has not been
			studied before. </ns2:techAbstractText>
		<ns2:healthCategories/>
		<ns2:researchActivities/>
		<ns2:researchSubjects/>
		<ns2:researchTopics/>
	</ns2:project>
	<ns2:project ns1:id="E37C97C5-7489-4205-834F-151D05B7E07A"
	             ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/projects/E37C97C5-7489-4205-834F-151D05B7E07A"
	             ns1:created="2016-11-11T20:42:55Z">
		<ns1:links test="helo2">
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/persons/AFFB5A85-DAC7-48F2-AE07-952481073BAA"
					ns1:rel="PI_PER"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/persons/DFA58FA2-CCD6-445F-B2BC-E830C23FA563"
					ns1:rel="COI_PER"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/persons/6E4302E7-A895-4FF7-AE8C-26C2478A82E6"
					ns1:rel="COI_PER"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/organisations/30A429E3-83B7-4E41-99C0-14A144F07DFE"
					ns1:rel="LEAD_ORG"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/organisations/FADDC755-1F45-47D7-8591-F183B7160CC2"
					ns1:rel="PP_ORG"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/organisations/E82E4BC6-2839-4E7A-82CA-88B033E53B45"
					ns1:rel="PP_ORG"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/organisations/F8B807ED-ACF2-4724-9DC6-291B77059637"
					ns1:rel="PP_ORG"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/funds/B7A4A2BB-1530-4846-8F2B-891EEBFF3F5F"
					ns1:rel="FUND" ns1:start="2013-10-01T00:00:00+01:00" ns1:end="2017-11-30T00:00:00Z"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/outcomes/keyfindings/45480FAD-42D9-4948-ADE2-1B161F6BF481"
					ns1:rel="KEY_FINDING"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/outcomes/disseminations/6E8F7769-1A48-4BDD-8248-6B5938CA3495"
					ns1:rel="DISSEMINATION"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/outcomes/impactsummaries/01F42709-4FC3-4267-9E2A-08591C7950F8"
					ns1:rel="IMPACT_SUMMARY"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/outcomes/publications/76690C2C-FEF9-42AC-A4A2-B09338B33C45"
					ns1:rel="PUBLICATION"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/outcomes/publications/7B0D46AB-374C-4327-9EFE-5CA9683560FB"
					ns1:rel="PUBLICATION"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/outcomes/publications/03415E7B-3BE0-4207-857D-B595F52E2C65"
					ns1:rel="PUBLICATION"/>
			<ns1:link
					ns1:href="http://gtr.rcuk.ac.uk:80/gtr/api/outcomes/publications/2D27AB50-6985-4A61-83C6-54A102DFCFB8"
					ns1:rel="PUBLICATION"/>
		</ns1:links>
		<ns2:identifiers>
			<ns2:identifier ns2:type="RCUK">NE/K001906/1</ns2:identifier>
		</ns2:identifiers>
		<ns2:title> Biogeochemistry, macronutrient and carbon cycling in the benthic layer </ns2:title>
		<ns2:status>Active</ns2:status>
		<ns2:grantCategory>Research Grant</ns2:grantCategory>
		<ns2:leadOrganisationDepartment>School of Ocean and Earth
			Science</ns2:leadOrganisationDepartment>
		<ns2:abstractText> The coasts and shelf seas that surround us have been the focal point of
			human prosperity and well-being throughout our history and, consequently, have had a
			disproportionate effect on our culture. The societal importance of the shelf seas
			extends beyond food production to include biodiversity, carbon cycling and storage,
			waste disposal, nutrient cycling, recreation and renewable energy. Yet, as increasing
			proportions of the global population move closer to the coast, our seas have become
			progressively eroded by human activities, including overfishing, pollution, habitat
			disturbance and climate change. This is worrying because the condition of the seabed,
			biodiversity and human society are inextricably linked. Hence, there is an urgent need
			to understand the relative sensitivities of a range of shelf habitats so that human
			pressures can be managed more effectively to ensure the long-term sustainability of our
			seas and provision of societal benefits. Achieving these aims is not straightforward, as
			the capacity of the seabed to provide the goods and services we rely upon depends on the
			type of substrate (rock, gravel, sand, mud) and local conditions; some habitats are
			naturally dynamic and relatively insensitive to disturbance, while others are
			comparatively stable and vulnerable to change. This makes it very difficult to assess
			habitat sensitivities or make general statements about what benefits we can expect from
			our seas in the future. Recently, NERC and DEFRA have initiated a major new research
			programme on Shelf Sea Biogeochemistry that will improve knowledge about these issues.
			In response to this call, we have assembled a consortium of leading scientists that
			includes microbiologists, ecologists, physical oceanographers, biogeochemists,
			mathematical modellers and policy advisors. With assistance from organisations like
			CEFAS, Marine Scotland and AFBI, they will carry out a series of research cruises around
			the UK that will map the sensitivity and status of seabed habitats based on their
			physical condition, the microbial and faunal communities that inhabit them, and the size
			and dynamics of the nitrogen and carbon pools found there. The latest marine
			technologies will measure the amount of mixing and flow rates just above the seabed, as
			well as detailed seabed topography. These measurements will allow better understanding
			of the physical processes responsible for movement and mixing of sediment, nutrient, and
			carbon. At the same time, cores will be retrieved containing the microbial and faunal
			communities and their activity and behaviour will be linked to specific biogeochemical
			responses. Highly specialised autonomous vehicles, called landers, will also measure
			nutrient concentrations and fluxes at the seabed. Components of the system can then be
			experimentally manipulated to mimic scenarios of change, such as changing hydrodynamics,
			disturbance or components of climate change. This will be achieved in the field by
			generating different flow regimes using a submerged flume or, in the laboratory, using
			intact sediment communities exposed to different levels of CO2, temperature and oxygen.
			By measuring the biogeochemical response and behaviour of the microbial and faunal
			communities to these changes, we will generate an understanding of what may happen if
			such changes did occur across our shelf seas. We will use all of this information to
			assess the relative vulnerability of areas of the UK seabed by overlaying the
			observation and experimental results over maps of various human pressures, which will be
			of value to planners and policymakers. Mathematical models will test future scenarios of
			change, such as opening or closing vulnerable areas to fishing or anticipated changes in
			the factors that control nutrient and carbon stocks. This will be valuable in exploring
			different responses to external pressures and for deciding which management measures
			should be put in place to preserve our shelf seas for future generations </ns2:abstractText>
		<ns2:potentialImpact> Commercial private sector and the knowledge economy: new and
			innovative methodologies, equipment and techniques, and combined state-of-the-art
			technologies (&gt;2.3 million in-kind, see JeS) will assess what the primary physical
			and biogeochemical controls of shelf productivity are up to shelf sea scales. Since many
			interests rely on the marine environment, beneficiaries will be varied. By sharing
			expertise and knowledge, a world-leading manufacturer of microsensors and microscale
			instrumentation and an internationally recognized marine environmental data acquisition
			company will benefit from exploitable opportunities, e.g. new visualisation tools that
			enable holistic understanding of large-scale ecosystem processes. Policy professionals,
			governmental and devolved governmental organisations: The importance of shelf seas to
			society extends beyond fisheries to wider issues, such as biodiversity, carbon cycling
			and storage, waste disposal, nutrient cycling, and renewable energy resources.
			Consortium expertise will contribute to these UK priority challenges. The UK Marine
			&amp; Coastal Access Act (MCAA), UK Climate Change Act, EU Habitats Directive and EU
			Marine Strategy Framework Directive (MSFD) support sustainable use of the marine
			environment. They also support the UK vision for achieving 'clean, healthy, safe
			productive and biologically diverse ocean and seas' (UK Marine Science Strategy). We
			will provide a coherent framework for sound evidence based-science in support of these
			policy instruments and statutory requirements. For example, the MSFD aims to achieve
			Good Environmental Status in EU marine waters by 2020, but we lack understanding of the
			magnitude and synchronicity of change in SSEs. Our research will directly inform
			Descriptor 1 (biological diversity) and 6 (seabed integrity) for a wide range of
			sediment habitats over time, which is important because the determination of good
			environmental status may have to be adapted over time (addressed in Task 2) &quot;in vie
			of the dynamic nature of marine ecosystems and their natural variability, and given that
			the pressures and impacts on them may vary with the evolvement of different patterns of
			human activity and the impact of climate change&quot; (MSFD). Our work will also inform
			environmental monitoring programmes: OSPARs Joint Assessment and Monitoring programme,
			the Eutrophication Monitoring Programme and The Clean Seas Environment Monitoring
			Programme (CSEMP, led by consortium member CEFAS). Task 1-3 complement the outcomes of
			CESEMP and provide scientific evidence to OSPAR. Similarly, experimental scenarios and
			modelling approaches will provide needed information for (i) the EU Water Framework
			Directive (the requirement for 'good chemical and ecological status' by 2015 does not
			account for climate change) and, (ii) the UK White Paper for MCAA (it is unclear how
			commitments to &quot;look ahead at the predicted impacts of climate change on the marine
			environment, how marine activities will contribute towards it, and how they are affected
			by it&quot; will be achieved). Finally, other EU instruments, such as the Habitats
			Directive (introduced in 1992), the EU Common Fisheries Policy (revised in 2002) and
			national legislation such as the UK MCAA and Scottish Marine Act, assume that removal
			(or control) of direct pressures will result in ecosystem recovery and/or species
			persistence. Our programme includes experimental scenarios and modelling approaches to
			provide further information on the vulnerability of SSEs in environmental futures under
			multiple pressures (Task 3). Our outputs will also help NERC meet its science theme
			challenges. Public, wider community: active engagement with a variety of organisations
			is detailed in Pathways to Impact (PtI). Skills&amp; training: In addition to academic
			progression, early career researchers will gain experience and receive mentoring in
			running a large interdisciplinary programme, as well as training in communication skills
			and scientific methodology </ns2:potentialImpact>
		<ns2:healthCategories/>
		<ns2:researchActivities/>
		<ns2:researchSubjects>
			<ns2:researchSubject>
				<ns2:id>138395</ns2:id>
				<ns2:text>Marine environments</ns2:text>
				<ns2:percentage>75</ns2:percentage>
			</ns2:researchSubject>
			<ns2:researchSubject>
				<ns2:id>46902</ns2:id>
				<ns2:text>Geosciences</ns2:text>
				<ns2:percentage>15</ns2:percentage>
			</ns2:researchSubject>
			<ns2:researchSubject>
				<ns2:id>13097</ns2:id>
				<ns2:text>Ecol, biodivers.&amp; systematics</ns2:text>
				<ns2:percentage>5</ns2:percentage>
			</ns2:researchSubject>
			<ns2:researchSubject>
				<ns2:id>33851</ns2:id>
				<ns2:text>Microbial sciences</ns2:text>
				<ns2:percentage>5</ns2:percentage>
			</ns2:researchSubject>
		</ns2:researchSubjects>
		<ns2:researchTopics>
			<ns2:researchTopic>
				<ns2:id>21005</ns2:id>
				<ns2:text>Sediment/Sedimentary Processes</ns2:text>
				<ns2:percentage>15</ns2:percentage>
			</ns2:researchTopic>
			<ns2:researchTopic>
				<ns2:id>143045</ns2:id>
				<ns2:text>Ecosystem Scale Processes</ns2:text>
				<ns2:percentage>15</ns2:percentage>
			</ns2:researchTopic>
			<ns2:researchTopic>
				<ns2:id>63200</ns2:id>
				<ns2:text>Biogeochemical Cycles</ns2:text>
				<ns2:percentage>60</ns2:percentage>
			</ns2:researchTopic>
			<ns2:researchTopic>
				<ns2:id>108367</ns2:id>
				<ns2:text>Community Ecology</ns2:text>
				<ns2:percentage>5</ns2:percentage>
			</ns2:researchTopic>
			<ns2:researchTopic>
				<ns2:id>80410</ns2:id>
				<ns2:text>Responses to environment</ns2:text>
				<ns2:percentage>5</ns2:percentage>
			</ns2:researchTopic>
		</ns2:researchTopics>
	</ns2:project>
</ns2:projects>