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Faculties & Departments
Department of Biology
National Institute for Cellular Biotechnology
The National Institute for Cellular Biotechnology (NICB) is a multi-disciplinary institute based in three third level colleges in the Dublin area. The constituent colleges are Dublin City University, the National University of Ireland Maynooth and the Institute of Technology Tallaght. The NICB is funded by the Higher Education Authority under PRTLI 3.
The main focus of the NICB is to understand cell function at a molecular level and to contribute to the prevention and treatment of disease.
The areas of research supported by the NICB include:
Cell Differentiation
Cell Biology of Cancer
Cell Biology of Microbial Diseases
Target Identification for Disease Diagnosis and Therapy
Molecules for Life
Bioethics and Public Perception of Biotechnology
Biological Applications of Computing
More information on the NICB may be found at www.nicb.ie
NICB AT NUI MAYNOOTH
NUI Maynooth is one of the constituent colleges of the NICB and the work of the NICB at NUI Maynooth takes place in the Department of Biology under the direction of Dr. Kevin Kavanagh and Dr. Sean Doyle. The main focus of the work at NUI Maynooth is aimed at the detection and treatment of fungal infections.
Further information on the work of Dr. Doyle and Dr. Kavanagh may be found at the Department of Biology website.
BACKGROUND TO PROJECTS
Fungal pathogens represent a significant cause of morbidity and mortality in patients immuno-compromised as a result of therapy or disease. Fungal pathogens are responsible for a large proportion of deaths among cancer and HIV+ patients and contribute to the range of fatal illnesses in those with respiratory distress. The two principal fungal pathogens (Candida albicans and Aspergillus fumigatus) are responsible for a range of superficial and systemic disease that can be difficult to control. C. albicans predominantly affects the mucosal sites in the body while A. fumigatus affect the pulmonary tissues in immuno-compromised patients. Part of the difficulty in treating conditions caused by A. fumigatus is the low level of successful detection of infection. In many instances diagnosis is delayed with a subsequent deleterious effect on patient survival.
MAIN OBJECTIVES
1. The first objective will be to use the presence of fungal toxins in serum or pulmonary secretions as indicators of Aspergillus infection. Existing diagnostic assays which rely upon detecting fungal cell wall constituents (glucans and galactomannans) in serum are ineffective and are partly responsible for the lateness of detection of disease. The Cell Culture/Monoclonal Antibody Core Facility at DCU will make an important contribution to this part of the project.
2. The second objective will be to characterise both the degradative enzymes and the non-ribosomal biosynthetic pathways leading to the synthesis of a number of the most important peptide toxins implicated in tissue invasion by A. fumigatus. Researchers at ITT (John Behan and Fintan Kelleher) will collaborate on the synthesis and mass spectrophotometric analysis of fungal toxin intermediates. Successful identification of both the key degradative enzyme activities and toxin biosynthetic processes will facilitate the development of novel means to circumvent metabolite-induced toxicity with a concomitant reduction in fungal pathogenicity. The proteomics and chemical analysis core facilities located at DCU will be important for this part of the NUIM project.
3. The third objective will be to assess the role of drug efflux pumps in conferring drug resistance in pathogenic fungi and establishing a means of reversing this phenomenon which can compromise patient recovery. This work will exploit the expertise in efflux pump studies available from the NICB Cancer Drug Resistance Research Group at DCU. Studies involving novel inhibitors of drug efflux pump action will be carried out in collaboration with Dr. Bríd Quilty, DCU.
PROJECT PERSONNEL
Dr. Emer Reeves
Using gene knock-out technology to examine role of NRP in pathogenicity of Aspergillus fumigatus.
Dr. Kathrin Reiber
Identification and characterisation of novel non-ribosomal protein synthesis in Aspergillus fumigatus.
Ms. Claire Neville
Role of non-ribosomal protein biosynthesis in fungi
Mr. Joe O'Keeffe
Assessment of role of drug efflux pumps in conferring anti-fungal drug resistance in pathogenic fungi.
Mr. Pat Geraghty
Role of mitochondrion in fungal pathogenicity and drug resistance
Mr. David Bergin
Development of novel in vivo pathogenicity testing systems. Insect immunology
Ms. Imelda Vickers
Role of proteases in pathogenicty of Aspergillus fumigatus
Ms. Rachel Geraghty
Identification and characterisation of GST in Aspergillus fumigatus
PUBLICATIONS – PEER REVIEWED
January 1, 2002 - October 31, 2003
1. Corcoran, A., Mahon, B.P. and Doyle, S. (2003) B cell memory is directed towards conformational epitopes of parvovirus B19 capsid proteins and the VP1-unique region. J Infect Dis. in press.
2. Fox, M., Gray, G., Kavanagh, K., Lewis, C. and Doyle, S. (2003). Detection of Aspergillus fumigatus mycotoxins: immunogen synthesis and immunoassay development. J Microbiol. Methods. in press.
3. O'Keeffe, J., Doyle, S. and Kavanagh, K. (2003). Exposure of the yeast Candida albicans to the anti-neoplastic agent Adriamycin increases the tolerance to Amphotericin B. Journal of Pharmacy and Pharmacology. in press.
4. Dalton, J.P., O'Neill, S.M., Stack, C., Collins, P., Walsh, A., Sekiya, M., Doyle, S., Mulcahy, G., Hoyle, D., Khaznadji, E., Moiré, N., Brennan, G.P., Mousley, A., Kreshchenko, N., Maule, A.G. and Donnelly, S.M. (2003). Fasciola hepatica cathepsin L-like proteases: biology, function, and potential in the development of first generation liver fluke vaccines. International Journal for Parasitology, 33(11):1173-1181.
5. CoyleB., Kavanagh K., McCann M., Devereux M. and Geraghty M. (2003) Mode of anti-fungal activity of 1,10-phenanthroline and its Cu(II), Mn(II) and Ag(I) complexes. Biometals 16: 321-329.
6. Geraghty, P. and Kavanagh, K. (2003) Erythromycin, an inhibitor of mitoribosomal protein biosynthesis, alters the Amphotericin B susceptibility of Candida albicans. Journal of Pharmacy and Pharmacology 55: 179-184.
7. Geraghty, P. and Kavanagh, K. (2003) Disruption of mitochondrial function in Candida albicans leads to reduced cellular ergosterol levels and elevated growth in the presence of Amphotericin B. Archives of Microbiology 179: 295-300.
8. Corcoran A, Mahon BP, McParland P, Davoren A and Doyle S (2003) Ex vivo cytokine responses against parvovirus B19 antigens in previously infected pregnant women. J. Med Virol. 70(3), 475-480.
9. Deegan O, Walshe K, Kavanagh K, and Doyle S. (2003) 'Quantitative Detection of C-Reactive Protein Using Phosphocholine – Labelled Enzyme or Microspheres.' Anal. Biochem. 312(2): 175-181.
10. Daly P and Doyle S (2003) Development of a Competitive PCR-ELISA for the detection of Equine Herpesvirus-1 (EHV-1). J. Virol Methods. 107: 237-244.
11. Daly P, Corcoran A, Mahon BP and Doyle S (2002) High Sensitivity PCR Detection of Parvovirus B19 in plasma. J. Clin. Microbiol. 40(6):1958-62.
12. Ellabib M, Agaj M, Khalifa Z and Kavanagh K (2002) Trichophyton violaceum as an important cause of tinea capitis in children in Tripoli (Libya): Results of a two year survey. Mycopathologia 153: 145-147.
13. Daly, P. & Kavanagh, K. (2002) Immobilisation of Aspergillus fumigatus colonies in a soft agar matrix allows visualisation of A549 cell detachment and death. Medical Mycology 40: 27-33.
14. Saldanda J, Lelie N, Yu MW and B19 Collaborative Study Group (incl. Doyle S and Daly P) (2002) Establishment of the first World Health Organisation International Standard for human parvovirus B19 DNA nucleic acid amplification techniques. Vox Sanguinis 82: 24-31.
15. Brennan M, Thomas DY, Whiteway M and Kavanagh K. (2002) Analysis of Candida albicans virulence in Galleria mellonella larvae. FEMS Immunology and Medical Microbiology 34 (2): 153-157.
16. Raab U, Beckenlehner K, Lowin T, Niller H-H, Doyle S and Modrow S (2002) NS1-protein of Parvovirus B19 interacts directly and via the transcription factors Sp1/Sp3 with the p6 promoter. Virology. 293(1):86-93.
17. Daly P, Collier T and Doyle S (2002)PCR-ELISA detection of Escherichia coli in milk. Letters in Applied Microbiology. 34(3):222-226.
18. Ellabib MS, Khalifa Z & KavanaghK. (2002) Dermatophytes and other fungi associated with skin mycoses in Tripoli, Libya. Mycoses 45: 101-104.
19. Ellabib M, Agaj M, Khalifa Z and Kavanagh K. (2002). Yeasts of the genus Candida are the dominant cause of onychomycosis in Libyan women but not men: Results of a two year surveillance study. British Journal of Dermatology 146: 1038-1041.
CONFERENCE PRESENTATIONS / POSTERS
2003
Shirley O’Keeffe, Des O’Leary, Sean Doyle, Cormac Kilty and Shane Kerr. The detection of parvovirus B19 in human sera using antigen-capture EIA. Society for General Microbiology (Irish Branch) NUI Maynooth, April 24/25 2003.
Bergin, D. & Kavanagh, K. Correlation between haemocyte density and fungal load in Galleria mellonella as indicators of fungal pathogencity. Society for General Microbiology (Irish Branch) NUI Maynooth, April 24/25 2003.
Delaney, S., Powell, F. & Kavanagh, K. Identification of bacterial species in Demodex folliculorum mites which may play a role in papulo-pustular rosacea. Society for General Microbiology (Irish Branch) NUI Maynooth, April 24/25 2003.
Geraghty, P. & Kavanagh, K. Mechanisms conferring amphotericin B tolerance in Candida albicans respiratory deficient mutants. Society for General Microbiology (Irish Branch) NUI Maynooth, April 24/25 2003.
Neville, C., Kavanagh, K., Reeves, E. & Doyle, S. Identification and characterisation of a putative non-ribosomal peptide synthetase (PES1) in Aspergillus fumigatus. Society for General Microbiology (Irish Branch) NUI Maynooth, April 24/25 2003.
O'Keeffe, J. & Kavanagh, K. Rapid RNA extraction from Candida albicans ATCC 10231. Society for General Microbiology (Irish Branch) NUI Maynooth, April 24/25 2003.
Reeves, EP, Doyle, S. & Kavanagh, K. Correlation between gliotoxin production and virulence of Aspergillus fumigatus in Galleria mellonella. Society for General Microbiology (Irish Branch) NUI Maynooth, April 24/25 2003.
Eshwika, A., Coyle, B., McCann, M. & Kavanagh, K. Metal based drugs alter susceptibility of the yeast Candida albicans to amphotericin B and miconazole. Society for General Microbiology (Irish Branch) NUI Maynooth, April 24/25 2003.
Claire Neville, Kevin Kavanagh, Emer Reeves and Sean Doyle. Identification and characterisation of a putative non-ribosomal peptide synthetase (pes1) in Aspergillus fumigatus. National Institute of Cellular Biotechnology, Department of Biology, NUI Maynooth, Co. Kildare. Society for General Microbiology (Irish Branch) NUI Maynooth, April 24/25 2003.
Elaine McCarthy, Sean Doyle, D. W. Halton, Aaron G. Maule, Colin Stack, Sheila Donnelly, and John P. Dalton. Functional expression and characterisation of a Schistosoma mansoni leucine aminopeptidase. Society for General Microbiology (Irish Branch) NUI Maynooth, April 24/25 2003.
Analysis of ex vivo cellular inflammatory immune response to B19 antigens by cDNA microarray analysis
Amanda Corcoran and Sean Doyle. National Institute for Cellular Biotechnology, Department of Biology, National University of Ireland, Maynooth, Co. Kildare. Society for General Microbiology (Irish Branch) NUI Maynooth, April 24/25 2003.
2002
Neville, C., Kavanagh, K. & Doyle, S. The role of Non-Ribosomal Peptide Synthesis in gliotoxin biosynthesis in Aspergillus fumigatus. Society for General Microbiology – Irish Branch Spring Meeting. Inst. Technology Carlow. March 26/27, 2002.
Neville, C., Kavanagh, K. and Doyle, S. Gliotoxin biosynthesis: a case of non-ribosomal peptide biosynthesis. Tenth International Congress of Mycology, Paris, France. July 27-August 1 2002.
O'Keeffe, J. & Kavanagh, K. Investigation of the role of the anti-neoplastic agent Adriamycin in conferring resistance to Amphotericin B in the pathogenic yeast Candida albicans. Society for General Microbiology – Irish Branch Spring Meeting. Inst. Technology Carlow. March 26/27, 2002.
Claire Neville, Kevin Kavanagh and Sean Doyle. The Role of Non-Ribosomal Peptide Synthesis in Gliotoxin Biosynthesis, a biocontrol agent against Pythium Damping-off disease. Irish Botanist's Meeting, NUI Maynooth, March 2002. (Awarded prize for best postgraduate oral presentation)
Delaney, S. Powell, F. Kavanagh, K. An investigation of the role of bacterial and Demodex-associated antigens in the induction of Rosacea. National Rosacea Society Research Workshop, Los Angeles, USA. May 15, 2002.
O'Keeffe, J. and Kavanagh, K. Mechanism conferring Amphotericin B tolerance in Doxorubicin B cultured Candida albicans. Tenth International Congress of Mycology, Paris, France. July 27-August 1 2002.
Claire Neville, Sharon Boyle, Sean Doyle, Frances Tinley and Kevin Kavanagh. Identification and cloning of three glutathione-S-transferase open reading frames from Aspergillus fumigatus. DCU, Glasnevin, Dublin 9. Sensing and signaling in microbial populations, SGM meeting, Sept. 2002.
Geraghty, P. & Kavanagh, K. Disruption of mitoribosomal function in Candida albicans leads to amphotericin B tolerance. Society for General Microbiology (Irish Branch) Autumn Meeting. Dublin City University, September 5 & 6, 2002.
Delaney, S., Powell, F.C. & Kavanagh, K. A potential role for bacterial antigens in the induction and persistence of Rosacea. Society for General Microbiology (Irish Branch) Autumn Meeting. Dublin City University, September 5 & 6, 2002.
Does Parvovirus B19 NS1 play a role in the selective deletion of B cells expressing anti-viral antibodies? Amanda Corcoran, Bernard P. Mahon and Sean Doyle. Poster Presentation. IX Parvovirus conference, Bologna, Italy. August 28-31, 2002.
Claire Neville, Sean Doyle and Kevin Kavanagh. Identification and charaterisation of events in the biosynthetic pathway of gliotoxin. NUI Maynooth, departmental seminar, Feb 2002.
Claire Neville, Sean Doyle and Kevin Kavanagh. Identification and characterization of key events in the biosynthetic pathway of gliotoxin in Aspergillus fumigatus. NUI Maynooth. Postgraduate research colloquium, March 2002.
Amanda Corcoran, Bernard P. Mahon Peter McParland, Anne Davoren and Sean Doyle. Towards determination of the influence of the maternal immune status on the susceptibility to parvovirus B19 during pregnancy. Oral presentation. IX Parvovirus conference, Bologna, Italy. August 28-31, 2002.
INVITED LECTURES
Kevin Kavanagh. "The mitochondrion as a target for novel anti-fungal drugs." School of Science, Institute of Technology Tallaght. Invited Research Seminar, March 25, 2003.
Kevin Kavanagh. "Novel approaches for the detection and treatment of fungal infections." Oral presentation of the Scientific Advisory Board of the National Institute for Cellular Biotechnology. Dublin City University, July 8, 2002.
Sean Doyle. Parvovirus B19: antibody-mediated and cellular immunity. Invited speaker. IT Tallaght, Tallaght, Dublin 24. April 2002.
Sean Doyle. "Emerging viral infections" Biology Today Conference for Second level students, NUI Maynooth. February 13, 2002.
Kevin Kavanagh. "The Biology of Human Fungal Pathogens". Presentation to Association of Second level Science Teachers of County Kildare. St. Mary's College, Naas, Co. Kildare. March 5, 2002.
Kevin Kavanagh. "Do Demodex mites cause Rosacea?" Biology Today Conference for Second level students, NUI Maynooth. February 13, 2002.
Sean Doyle. Plasma Derivatives Meeting, Brussels Belgium, March 2001. " B19 virus".
RESEARCH AWARDS
1. "Use of anti-sense technology to assess the role of glutathione s-transferase in fungal virulence". Basic Research Grant Programme Euro166,000. (S. Doyle, K. Kavanagh, E. Reeves) 2003-2006.
2. Society for General Microbiology Summer Studentship to Mr. Frank Roche. (2003). Stg£1600. (S. Doyle)
3. Health Research Board Summer Studentship to Ms Sharon Boyle (2002). Euro 1200 (S. Doyle)
4. "An investigation of the role of bacterial and Demodex associated antigens in the induction of Rosacea." National Rosacea Society (USA) (2002 – 2004) $23,500. (K. Kavanagh)
5. "Novel Immuno-diagnostics for the Detection of Aspergillus Infection" Advanced Technology Research Programme (Enterprise Ireland) (2001 - 2004) £202,000. (K. Kavanagh and S. Doyle)
6. "Design, Synthesis, Purification and Evaluation of Pharmaceuticals as Chemotherapeutics and Anti-microbials" Euro 317,000 (2002 - 2006) (K. Kavanagh in association with researchers in Dublin and Tallaght Institutes of technology.
CONFERENCES ORGANISED
Society for General Microbiology – Irsh Area Section Conference: ‘Microbial Diseases in the Immunopompromised Patient’. NUI Maynooth, 24-25th April 2003. Organiser: Dr Sean Doyle.
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