Below is a summary of research projects which I am involved or have been involved in previously. My main area of research at the moment is animal models of infection, in particular chronic pulmonary infection of mice with Pseudomonas aeruginosa as a model for infection in CF patients.

T-cellepitope mining of the Pseudomonasaeruginosa proteome for novel vaccine targets- Queen’s University Belfast

Pseudomonas aeruginosais the most common bacterial species infecting the lungs of cystic fibrosis(CF) patients, with 80% of adult patients infected. I am undertaking alarge-scale screen of P. aeruginosaproteins to identify novel vaccine targets. I will express a subset of 200proteins (virulence factors, those differentially expressed in biofilm,secreted and cell surface proteins).  Iwill then look for T cell responses to the proteins in blood from CF patientsusing an ELISpot assay simultaneously detecting IFN-γ and IL-17. Proteinsinducing a T cell response will be further analysed by intracellular flowcytometery, thus also allowing detailed characterisation of the responding Tcells. This project will offer new insights into interactions that occurbetween bacteria and the adaptive immune system during chronic infection withthe potential for identification of novel vaccine targets.

Comparative proteomic analyses of Helicobacter pylori strains fromchildren with and without iron deficiency-Trinity College Dublin

Helicobacter pyloriinfection is associated with iron deficiency (ID) likely due in part tosequestration of host iron by the pathogen which can inhibit iron absorption bythe host.  To colonise successfully, H. pylori must compete with the host forbio-available iron and iron availability modulates protein expression by thepathogen.   The aim of this study was toidentify changes to the proteome of ID and non-ID-associated isolates of H.pylori when cultured under the iron-restricted conditions encountered invivo.  Multiple H. pylori proteinswere differentially expressed when the pathogen was cultured underiron-restriction compared with iron-replete conditions, including adhesins,OMPs, virulence and colonisation factors. These data demonstrate differentialprotein expression profiles between ID and non-ID associated H. pyloriisolates when cultured under iron-restricted conditions.  I presented the results of this study at theCONTENT consortium meeting in Uruguay.  Amanuscript is currently in preparation.

The role of Tyk2 during the innate immuneresponse to Listeria monocytogenes-University of Veterinary Medicine, Vienna.

The Janus Kinase-signaltransducers and activators of transcription (JAK-STAT) signalling pathway is amajor component of the innate immune response, allowing efficient signaltransduction from cell surface receptors to target genes.  By infecting C57BL6 WT and Tyk2-/- mice Ihave shown that Tyk-2, a non-receptor tyrosine kinase is essential forprotection of mice against systemic infection with L. monocytogenes.  Inaddition, I showed that infection of mice which had the gene for a kinaseinactive variant of Tyk2 were resistant to infection indicating akinase-independent signalling mechanism.

Proteomic characterization of Leptospira interrogans in the urine ofchronically infected hosts-University College Dublin

Leptospirosis is a zoonotic disease caused bypathogenic species of the genus Leptospira.Leptospira asymptomatically colonizethe renal tubules of maintenance hosts such as rats, from where they are shedinto the environment during urination. Humans and other susceptible mammalsoften develop acute infection following contact with contaminated urine. Theprimary goal of this study was to examine how Leptospira survive in the renal tubules of experimentally infectedrats despite a specific antibody attack by the host. Using a variety ofproteomic techniques, my novel findings which were published in Infection andImmunity indicated that Leptospiradownregulate antigen expression in order to evade the antibody responseelicited by the host during chronic infection. In addition, this article was selected for the Infection and Immunity‘Spotlight’ edition, a section reserved for particularly meritorious work.

“Proteomic analysis of Leptospira interrogans shed in urine of chronically infected hosts”. Avril M. Monahan, John J. Callanan, and Jarlath E. Nally.

Infection and Immunity, November 2008, Vol. 76 (4952-4958).

*This article was chosen for the Infection and Immunity “Spotlight” feature, a section which includes short descriptions of especially meritorious articles. 

Review Paper:  “Leptospirosis: risks during recreational activities”.

Avril M. Monahan, Ian S. Miller and Jarlath E. Nally.  Journal of Applied Microbiology, September 2009, Vol. 107 (707-716).

Invited Review Paper:  “Host-pathogen interactions in the kidney during chronic leptospirosis”.  Avril M. Monahan, John J. Callanan and Jarlath E. Nally.

Journal of Veterinary Pathology, September 2009, Vol. 46 (792-799)

“Detection and quantification of leptospires in urine of dogs; a maintenance host for the zoonotic disease leptospirosis”. Pablo D. Rojas, Avril M. Monahan, Simone Schuller, Ian S. Miller, and Jarlath E. Nally.

European Journal of Clinical Microbiology & Infectious Diseases, 2010, Vol 29 (1305-1309).

“Potent innate immune response to pathogenic Leptospira in human whole blood”.  Goris MG, Wagenaar JF, Hartskeerl RA, van Gorp EC, Schuller S, Monahan AM, Nally JE, van der Poll T, van 't Veer C.

PloS ONE, 2011, Vol 31 (e18279).

“Comparative proteomic analysis of differentially expressed proteins in the

urine of reservoir hosts of leptospirosis”.

PLoS ONE, 2011, 6(10): e26046