Conference of University Rectors in Ireland : University Collaboration Biochemistry

Biochemistry

Universities Involved Trinity College Dublin
Queen's University Belfast

Department(s) Biochemistry

Project Title / Description
Design and synthesis of inhibitors of thyrotropin releasing hormone (TRH) degrading ectoenzyme for use in assessing the role of this enzyme and TRH in the CNS.

Contact between Dr Kelly and Dr Williams was first made at a meeting of the biochemical society in the UK. The main objective of the project is to design and synthesise inhibitors of the neuroeptidose, thyrotropin releasing hormone degrading ectoenzyme.

The following have been published Kelly, JA, Slator, GR, Tipton, KF, Williams, GH, and Bauer, K. Development of a continuous, fluorometric coupled enzyme assay for thyrotropin releasing hormone degrading ectoenzyme.
Anal. Biochem. 274, 195202, 1999.

Contacts Dr Julie A Kelly, Principal Investigator,
Trinity College Dublin
Tel + 353 1 608 1604
Kellyja@tcd.ie Dr Carvell William
Tel 04890 272064
c.williams@qub.ac.uk

Development Potential
Dr Kelly plans to submit an application to the Wellcome Trust in the first half of 2000 for continued funding for this line of research.

Universities Involved	University College Dublin University of Ulster, Coleraine
Department(s)	Biochemistry
Project Title / Description	A study of diabetic patient serum induced inhibition of insulin secretion from clonal pancreatic ßcells. Collaborative research initiated in 1996. Objectives: Studies of the effect of diabetic patient sera on insulin secretion from pancreatic bcells. Completed June 1999. Outcome: Peer reviewed scientific paper published in the Journal of Endocrinology. Conroy SJ, AbdelWahab YHA, Caraher CM, Byrne PM, Murphy E, Nolan J, Flatt PR and Newwsholme P (2000). Evidence for complementdependent and independent inhibition of insulin secretion from clonal ßcells incubated in the presence of newly diagnosed IDDM patient sera. J Endocrinol 164: 139147. Activities: Joint work in the laboratories of Dr Newsholme (UCD) and Prof. Flatt (University of Ulster).
Funding Bodies	Health Research Board, Enterprise Ireland and international collaboration funding.
Contacts	Philip Newsholme Tel + 353 1 706 1551 Fax + 353 1 283 7211 philip.newsholme@ucd.ie
Development Potential	The project now supported by a HRB NorthSouth Cooperation grant (19992002). The grant supports a graduate student who is working an equal amount of time in both laboratories.

Universities Involved	University College Dublin Queen's University Belfast
Department(s)	Biochemistry
Other Universities	Tufts University, Massachusetts, USA
Project Title / Description	Stabilisation of tetrahedral adducts by the serine proteases Proteolytic enzmes such as the thoil and serine proteases have a wide range of biological phenomena including fertilisation, bleeding disorders, emphysema, heart attack, hormones activation, digestion, the immune response etc. Consequently there is considerable interest in understanding the mechanism of action of these enzymes and in their specific inhibition. It is thought that the serine proteases get much of their catalytic efficiency from stabilising the tetrahedral intermediates formed in the catalysis. But because tetrahedral intermediates do not accumulate during catalysis they cannot be directly studied. One solution to this problem is the study transition state analogues which mimics the tetrahedral intermediates formed during catalysis. Specific 13/cenrichment of such inhibitors allows us to use 13/cnmr to identify and characterise a single carbon atom within an enzymeinhibitor adduct. In this project it is intended to use this approach to study the stabilisation of the tetrahedral adducts by the serine proteases. It is also intended to determine the 3Dstructure of these inhibitors bound to the enzyme. The Project is open to new collaborators. Output so far four publications.
Funding Bodies	An Enterprise Ireland Grant from the Scientific Research Programme. IR£35,500
Contacts	Prof. Bill Bachovchin Tel (617) 636 6867/6409 wbachovc@OPAL.TUFTS.EDU	Prof. Brian Walker Tel 04890 272117 brian.walker@qub.ac.uk
Development Potential	Yes

Universities Involved	University College Dublin University of Ulster
Department(s)	Biochemistry
Project Title / Description	Identification of the mechanisms involved in IDDM (Insulin Dependent Diabetes Mellitus) patient sera induced inhibition of sscell
The activities were	A. Investigations of immune factors involved in the pathogenesis of Type I diabetes (IDDM) and mechanisms of immunemediated pancreatic sscell dysfunction and death. B. Regulation of phagocytic immune cell function by dietary factors and hormones.
Contacts	philip.newsholme@ucd.ie

Universities Involved	National University of Ireland, Galway Queen's University Belfast
Department(s)	Biochemistry
Project Title / Description	Cathepsin B Inhibitors Cathepsin B is a cysteine protease that plays a pitvotal role in a broad range of diseases including rheumatoid arthritis, cancer and septic shock. These are debilitating diseases which, in the later two cases, are often fatal. Therefore the proteases has obvious Biomedical and social importance. The proposed programme of research aims to harness the powerful methodology of combinatorial peptide synthesis for the generation of a novel series of inhibitors of this protease. These inhibitors may form the basis for the development of therapeutic agents for the amelioration of the diseases. Additionally, the kinetic information derived from the study may also prove useful for the design of different template molecules with enhanced therapeutic potential. Consequently, both the inhibitors and the kinetic information revealed as part of the project, could be the subjects of many future patent applications. The project is quite demanding and requires the input of an experienced Postdoctoral bioorganic chemist or Biochemist with an interest in peptide synthesis and expertise in enzymology and protein purification. Funding from Enterprise Ireland. Most costs relating to Postdoctoral Biochemist appointment and consumables.
Contacts	Prof. B Walker Tel 0801 232 272117 Brian.walker@qub.ac.uk	Dr Chris Laffey, NUI, Galway
Development Potential	Yes other allied projects on the same lines. (i.e. using Synthetic Peptides).

Universities Involved	Trinity College Dublin Queen's University Belfast
Department(s)	Biochemistry
Project Title / Description	Design and synthesis of inhibitors of thyrotropin releasing hormone (TRH) degrading ectoenzyme for use in assessing the role of this enzyme and TRH in the CNS. Contact between Dr Kelly and Dr Williams was first made at a meeting of the biochemical society in the UK. The main objective of the project is to design and synthesise inhibitors of the neuroeptidose, thyrotropin releasing hormone degrading ectoenzyme.
The following have been published	Kelly, JA, Slator, GR, Tipton, KF, Williams, GH, and Bauer, K. Development of a continuous, fluorometric coupled enzyme assay for thyrotropin releasing hormone degrading ectoenzyme. Anal. Biochem. 274, 195202, 1999.
Contacts	Dr Julie A Kelly, Principal Investigator, Trinity College Dublin Tel + 353 1 608 1604 Kellyja@tcd.ie	Dr Carvell William Tel 04890 272064 c.williams@qub.ac.uk
Development Potential	Dr Kelly plans to submit an application to the Wellcome Trust in the first half of 2000 for continued funding for this line of research.