Biomedical Science

 

Universities Involved

University College Dublin
Queen's University Belfast

Department(s)

Pharmacology

Other Universities

University of Ulm (Denmark)

Project Title / Description

Catecholamine­mediated regulation of lymphatic vessels (Key words: lymphatics; smooth muscle; adenylyl cyclase; catecholamines; 5­HT).

The objective of this study was to investigate plasma membrane signalling by catecholamines in cells cultured from bovine mesenteric lymphatic smooth muscle. Cell cultures were established and characterised by electron microscopy and immunofluorescent staining for smooth muscle a­actin. Evidence was not obtained for binding by a2­ or a1­adrenergic ligands to whole cells or to derived plasma membranes. Forskolin concentration­dependently stimulated adenylyl cyclase (AC) activity in plasma membranes and guanine nucleotide analogues also augmented basal and forskolin­stimulated activities. No effect of catecholamines, phenylephrine or clonidine was observed on basal or forskolin­stimulated activity. Under assay conditions favouring activation of inhibitory G­proteins, basal AC activity was again concentration­dependently increased by guanine nucleotide. Pertussis toxin treatment of whole cells did not alter basal or stimulated membrane AC activities.

Limited evidence was obtained for low affinity binding of [3H]5HT to whole cells and plasma membranes. [3H]Thymidine incorporation into cellular DNA was stimulated by 5­HT or by the 5­HT1A receptor­selective agonist 8­OHDPAT. High concentrations of the 5­HT1 receptor antagonist methiothepin inhibited basal, 5­HT­ and 8­OHDPAT­stimulated [3H]thymidine incorporation. Lastly no inhibition of basal or forskolin­stimulated AC activity by 5­HT or 8­OHDPAT was observed under conditions favouring activation of inhibitory G­proteins.

It is concluded that bovine lymphatic smooth muscle cells express a plasma membrane AC which is not linked to measurable catecholamine receptors, but which is subject to regulation by guanine nucleotides via the stimulatory Gs protein, or directly by forskolin. No evidence was found for a linkage of inhibitory G­proteins to AC; limited evidence has been presented for a possible mitogenic effect of 5­HT, mediated by 5­HT1 receptors


Universities Involved

Trinity College Dublin
The University of Ulster, Coleraine

Department(s)

Clinical Medicine

Project Title / Description

The effect of folate deficiency on DNA breaks in human colonic mucosa.

This project is with the University of Ulster. This study is to assess the presence or absence of folate deficiency in the colonic mucosa of patients with colonic polyps or colonic cancer. We also wish to see whether giving low dose folic acid supplementation can significantly increase the level of colonic mucosal cell folate content and also reduce the likelihood of colonic mucosal cancer developing. The project started in 1998 and will run until 2002.

Contacts

Prof. DG Weir
Tel + 353 1 608 2100/353 1 454 2043
dweir@tcd.ie

 

 

Development Potential

The University of Ulster are experts in Nutrition with a special interest in the effects of folate. They also have a laboratory which is renowned for its work in Comet assays of DNA breakes.


Universities Involved

Trinity College Dublin
Queen's University Belfast

Department(s)

Ocular Genetics Unit

Project Title / Description

Diseases of Visual Impairment

This has been a collaboration with Dr Julie Sylvestri, Dept of Ophthalmology, over the tracing of families with forms of glaucoma. Both glaucoma and retinitis pigmentosa are common causes of registered blindness.

Publication arising from the collaboration

Farrar GJ, Kenna P, Redmond R, McWilliam P, Bradley D, Humphries MM, Sharp P, Ingkehearn C, Bashir R, Jay M, Watty A, Ludwig M, Schinzel A, Sammans C, Gal A, Bhattacharya S and Humphries P, Autosomal dominant retinitis pigmentosa (RP4): absence of the rhodopsin codon 23 proline­>histidine transversion in pedigrees of European origin. American Journal of Human Genetics, 47, 941­945, 1991.

Farrar GJ, Kenna P, Redmond R, McWilliam P, Bradley D, Humphries MM, Sharp EM, Fishman G, Marchese C, Fusi L, Dufier JL, Abitbol M and Humphries P, Autosomal dominant retinitis pigmentosa (RP4): analysis of mutations within the rhodopsin gene. Retinitis Pigmentosa: Advances in Clinical and Genetic Research. (Pbl. CRC Press, Florida: Eds. Humphries P, Bhattacharya S and Bird A), 1991.

Contacts

Dr Julie Sylvestri, Dept Ophthalmology
Queen's University Belfast

Development Potential

Yes. There have been discussions with Dr Roger Anderson, Department of Optometry, University of Ulster over possible areas of future collaboration.


Universities Involved

Trinity College Dublin
University of Ulster, Coleraine

Department(s)

Biomedical Science

Project Title / Description

Bioavailability of 5 methyltetrahydrofolate

2000­2004 duration. New collaborators cannot join as project is on­going. Main objective of project is to determine the bioavailability of 5 methyltetrahydrofolate. Resources are 400,000 ECU. Project funded
by 5th Framework program EU.

Contacts

Dr Helene McNulty
Tel 04890 324583

 

 


Universities Involved

Trinity College Dublin
University of Ulster, Coleraine

Department(s)

Biomedical Science

Project Title / Description

Bioavailability of folic acid and food folates

1999­2002 duration. New collaborators cannot join as project is on­going. Main objectives of project are to determine the bioavailability of folic acid and food folates in man, and determine the differences in bioavailability of food folates and folic acid. Main outcomes are to be published. Resources are IR£1.0m. Project funded by Ministry of Agriculture, Fisheries and Food U.K. (MAFF).

Contacts

Dr Helene McNulty
Tel 04890 324583

 

 

Development Potential

MAFF have ongoing funding for projects in the role of folic acid in preventing colorectal cancer.


Universities Involved

University College Dublin
Queen's University Belfast

Department(s)

Pharmacology, School of Biomedical Science

Project Title / Description

Catecholamine regulation of lymphatic vessel function.

This was an EU funded project, under the second Framework SCIENCE programme: There were three participants: Prof. McHale QUB; Dr A Keenan, UCD; Prof. P Gierschik, University of Ulm Germany.

Outputs were a number of abstracts, a full research paper, one PhD student trained. One postdoctoral research fellow employed.

Contacts

Prof. NG McHale, QUB
Tel 04890 335794

 

 

Development Potential

Informal discussions have taken place regarding future possible co­operation.


Universities Involved

Dublin City University
University in Ulster, Jordanstown

Project Title / Description

The biomedical and environmental sensor technology (BEST) centre.

The BEST centre was established in 1995 with grant aid assistance from the International Fund for Ireland. The centre is a distributed network of research centres combining the sensor expertise of sensor research groups across the island of Ireland. Currently the centre represents a partnership between the Northern Ireland Bio­Engineering Centre (NIBEC), UU, and the National Centre for Sensor Research (NCSR) at DCU. The centre was funded until 1998 by the IFI and since then has been supported from internal resources by the two research centres.

The project's primary objective is the promotion of vibrant biomedical and environmental sensor industry in Ireland through close collaboration with industry and the research centres.

Contacts

Dr Declan Raftery
Tel + 353 1 704 5847/8021
Declan.raftery@dcu.ie

Prof. Malcolm Smyth
Tel + 353 1 704 5308/5503
Malcolm.smyth@dcu.ie

Prof. Dermot Diamond
Tel + 353 1 704 5454/8021
Dermot.diamond@dcu.ie

 

Prof. Brian MacGraith
Tel + 353 1 704 5299
gdm@physics.dcu.ie

 

 

Business Involvement

As this is a collaborative centre, there are a number of industrial partners involved in a range of collaborative R&D projects.


Universities Involved

University College Cork, Ireland
Queen's University Belfast

Department(s)

Department of Pharmacology and Therapeutics, Dept of Biochemistry

Project Title / Description

Intracellular Processing of Bile Salt­Stimulated Lipase prior to secretion.

Identification and characterisation of the cognate proteoglycan for PCE/BSSL.

Pancreatic cholesterol esterase (PCE) and Bile Salt­stimulated Lipase (BSSL) are members of the lipased­superfamily of proteins and share identical primary structures. They are heparin­ binding proteins that are widely distributed in tissues and among species. Sources include pancreatic tissue and juice, mammary gland and milk. PCE/BSSL is detected by Northern blot in liver. It is present in insulinoma, hepatocarcinoma, panreatic carcinoma cell lines, and eosinophils. PCE/BSSL activity is found in human placenta, rat and rabbit heart, rat and rabbit aorta, and in the plasma of a variety of species including man. PCE/BSSL
is secreted by human macrophage­monocytes and is present in atheroma. Little work has been done on the processing of PCE/BSSL prior to secretion. It is proposed to study aspects of intracellular processing of the lipase using molecular and protein chemistry techniques. The objective is to study the nature of the Proteoglycan to which PCE binds. To achieve this objective the gene for human PCE and cDNA for the human, rabbit, and bovine PCE is required as well as purified human BSSL to homogeneity.

First contact was made by e­mail after literature review.

It is hoped to gain Wellcome funding.

On­site resources are available for tissue culture, molecular and protein chemistry techniques.

Contacts

Dr Niall Colwell, UCC
Tel +353 21 904238
n.colwell@ucc.ie

Dr MMT O'Hare, QUB
Tel 048 90 240503 Ext. 2605
Fax 048 90 236455
m.ohare@qub.ac.uk

Prof. Brian MacGraith
Tel + 353 1 704 5299
gdm@physics.dcu.ie

Development Potential

The project is open to new collaborators. In particular, Dr BV Kumar of St Louis MO USA, has expressed interest in the project. Dr Kumar has worked on regulation of the gene expression for PCE in a rabbit model.


Universities Involved

University of Ulster
Trinity College Dublin

Department(s)

Radiation Science Group
School of Biomedical Science

Project Title / Description

Selective activation of transgenes to enhance radiotherapy in prostate cancer.

It is hoped to complete this gene therapy based project In 2004 providing adequate funding is obtained from HPSS/HRB. This project is open to new collaborations.

The aims of this North/South co­operation are to:

  • Establish a North­South group to advance research into molecular therapies for prostate cancer.
  • Strengthen the overall quality of the research of each group by contributing new skills to existing areas of expertise.
  • Provide a conducive environment for young Irish Scientists to learn new skills/techniques.

The genesis of the collaboration resulted from a presentation given by myself on the development of X­ray inducible promoters at the Irish Association of Cancer Research in Belfast 1999.

Two meetings have taken place since this time to plan the details of a collaborative project, involving presentations from the Northern and Southern partners on work to date and the development of a co­operative strategy for future research.

A series of GFP expressing plasmids which have been used in preliminary experiments to investigate the delivery of tissue specific expression promoters to prostate tissue, have been given to TCD. TCD has agreed
to provide UU with access to the microarray facility which is currently being developed as a Technology Platform.

Since this time an application, has been lodged, for an HPSS North/South grant to help fund this collaboration. Both groups at present are currently investigating genetic pro­drug activating therapy approaches for the treatment of cancer. UU obtained a grant from the CRC to investigate a novel bio­reductive drug, AQ4N by delivery of cytochrome p450 under the control of X­ray inducible promoters.

TCD has obtained funding from HRB to pursue a gene therapy approach to increase pro­drug activation specifically in prostate tumours using prostate specific promoter and enhancer elements.

A collaborative project would enhance the overall quality of the research of both partners. It is hoped to use a dual promoter incorporating both X­ray inducible and prostate specific elements to target prostate tumours using a pro­drug activation approach.

Contacts

Dr Mark Lawler
Tel + 353 1 608 2093
Fax + 353 1 410 3428
mplawler@tcd.ie

Prof. Donal Hollywood
Tel + 353 1 497 4552
Fax + 353 1 410 3428
dhlywood@tcd.ie

 

Development Potential

Yes, provided there is funding from HPSS/HRB. At present the current grants are funding this collaboration. However, funding specifically for this collaboration would allow for development in this area.


Universities Involved

University College Cork
Queen's University Belfast
University College Dublin

Department(s)

Department of Biochemistry

Project Title / Description

Identification of susceptibility genes for progressive renal disease by combined genotyping for single nucleotide polymorphisms and analysis of differential gene expression.

Diabetic nepropathy and IgA nephropathy are major causes of end stage renal failure.

Glomerulosclerosis is a central pathological feature of both diseases and results, in large part, from mesangial cell dysfunction. Here, it is proposed to identify susceptibility genes for glomerulosclerosis by combining (a) genotyping of DNA from patients with diabetic nephropathy and IgA nephropathy for single nucleotide polymorphisms and mutations with (b) analysis of differential gene expression in models of these diseases in vitro. This collaborative project will bring together complementary expertise from three centres to create a research programme that is significantly stronger than the sum of its component parts. Dr Maxwell's research group at the Queen's University of Belfast has extensive expertise in molecular epidemiology and role of polymorphisms in the pathogenesis of renal disease. Professor Brady's group at University College Dublin has recently established the utility of suppressive subtractive hybridisation (SSH) as a methodology for identifying pro­glomerulosclerotic genes in renal cell culture systems in vitro. Dr McCarthy's group at University College Cork has recently established the exciting technique for rapid high throughput genotyping of human DNA for polymorphisms and mutations in disease susceptibility genes. Our long term goal
is to identify molecular mechanism of glomerulosclerosis that can be targeted for therapeutic gain.

Contacts

Dr T McCarthy, UCC
Tel + 353 21 904009
Fax +353 21 274034
t.mccarthy@ucc.ie

Professor Hugh R Brady, Coordinator, UCD
Tel + 353 1 830 7419
Fax + 353 1 830 8404
hrbrady@mater.ie

Dr A Peter Maxwell, QUB
Tel 048 90 32 924
Fax 04890 26 3535
a.p.maxwell@qub.ac.uk


Universities Involved

University College Cork
Queen's University Belfast

Department(s)

Department of Biochemistry

Other Universities

Karolinska Institute, Stockholm, Sweden
Netherlands' Institute for Brain Research, Amsterdam, The Netherlands

Project Title / Description

Investigation of the influences of presenilin­1 on amyloid precursor protein metabolism and to examine if this modulation is regulated by protein kinase C?

The project combines the complementary skills of biomedical research groups North and South. Its overall objective is to understand biological phenomena and mechanisms which cause the neurodegeneration that results in Alzheimer's disease. The outcome is expected to provide a greater understanding of what causes Alzheimer's disease with a view to being able to develop treatments to ameliorate the devastating symptoms of this brain disorder.

Specifically the present project is investigating how brain signals control the metabolism of the beta amyloid precursor protein. Original contact was made when the two major participants Dr C O'Neill and Dr J Johnston worked together in an Alzheimer's Disease research centre at the Karolinska Institute in Sweden.

The project is funded by the Health Research Board of Ireland over three years (Dec. 1998 ­ Dec. 2001) to the value of £68,000. A post graduate student Rebecca Griffin is employed to conduct the research work.

The project collaboration is progressing very satisfactorily with one publication being prepared for submission and the research work will be presented at the American Society for Neuroscience. The research collaborators are in constant contact by e­mail and through visits between North­South to plan and discuss work, learn and develop complementary expertise and also to give seminars.

Contacts

Dr Cora O'Neill
Tel + 353 21 904122 Fax + 353 21 274034
c.oneill@ucc.ie

Dr Janet Johnston, QUB
Tel 04890 272100 Fax 04890 236505
j.a.johnston@qub.ac.uk

 

Development Potential

Yes, there is very strong potential for this. In fact, the major collaborating partners have very recently submitted another more expansive grant to the Health Boards HRB­HPSS including more interacting groups north and south. This application has the same overall aim namely the understanding of the molecular mechanisms which cause the brain to degenerate in Alzheimer's disease. However, the research input is much more broadly focused including clinical groups both North (Dr C Foy, Belfast City Hospital) and South (Prof. D Coakley, St. James Hospital, Dublin) and two clinical geneticists (Dr S McIlroy, QUB and Dr T McCarthy, UCC).


Universities Involved

University of Ulster, Coleraine

University College Cork

Department(s)

Northern Ireland Centre for Diet and Health (NICHE)

School of Biomedical Sciences

Project Title / Description

Synbiotics and cancer prevention in humans

 

Start 2000

Finish 2003

 

Contact made via existing collaborations

No further collaborators are possible under EU contract.

 

The overall aim of the proposal is to evaluate the potential cancer-preventing activity of pro- and pre-biotic (‘SYNBIOTIC’) combinations in human volunteers. The results from the project will contribute to the formulation of improved dietary advice for Europeans.

 

The project involves in vitro experiments, studies in animal models and an intervention study in human volunteers to establish whether combinations of pro and prebiotics have cancer preventing potential.

 

The project consortium is complete and hence not open to new collaborators.

 

Project funded by EC

(5th Framework programme)

Contacts

Prof. J K Collins

Tel + 353 21 902 642

Fax + 353 21 903101

Prof. Sean Strain

NICHE

University of Ulster

Coleraine, BT52 1AA

Tel 04870 324795

Fax 04870 323023

jj.strain@ulst.ac.uk

Prof. P Morrissey

Dept of Nutrition

University College Cork

Tel + 353 21 902406

Fax +353 21 270244

p.morrissey@ucc.ie

 

 

Prof. M Gibney

Trinity Centre for Health Sciences

St James Hospital

Dublin 8

Tel + 353 1 608 2102

Fax + 353 1 454 2043

mgibney@tcd.ie

 

 

Development Potential

Other collaborative projects in this area have been submitted to EU.

 


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