 |
 |
 |
 |
 |
 |
 |  |  |
 |
Faculties & Departments
Department of Biology
Dr. Martina Schroeder
Head of Laboratory
Host-Pathogen Interaction Laboratory
- Dr. Martina Schroeder
- Tel: (353-1) 708 6358 or 6285222 ext. 3244; Fax: (353-1) 708 3845
- e-mail: martina.schroeder@nuim.ie
- Research Profile
Research interests:
Viral recognition by pattern recognition receptors:
Viral recognition by the innate immune system is mainly mediated by two classes of pattern recognition receptors: endosomal Toll-like receptors (TLRs) and cytoplasmic RIG-like helicases (RLHs). Both classes detect viral nucleic acids and lead to the induction of type I interferons, which are potent anti-viral mediators. This requires activation of the NF-kB, IRF3/7 and AP-1 transcription factors. Signalling pathways connecting the anti-viral PRRs to transcription factor activation and interferon induction are beginning to be elucidated, and the lab hopes to contribute to their understanding.
A lot of viruses have developed sophisticated mechanism to evade detection by PRRs and/or to actively inhibit the resulting signalling pathways in order to prevent transcription factor activation and the induction of pro-inflammatory and anti-viral mediators. Studying viral immunoregulatory proteins has often led to the discovery of novel aspects or mediators of the human response against the virus. For example, by studying the poxvirus protein K7 we have recently identified its host target, the human DEAD-box helicase DDX3, as a novel mediator of IRF3 activation and interferon induction (Schroder et al. EMBO J 2008).
The human DEAD-box helicase DDX3 as a viral target:
DDX3 is now a major research focus of the lab, due to the fact that it seems to be a major target for viruses. In addition to poxviruses, at least two other viruses that pose major global health threats also interact with DDX3: HIV rev protein interacts with DDX3 for the purpose of shuttling its mRNAs out of the nucleus and DDX3 was hence shown to be required for HIV replication (Yedavalli et al. 2004). DDX3 also seems to be targeted by the Hepatitis C virus (HCV) Core protein and be required for HCV replication (Ariumi et al. 2007). Due to these findings, DDX3 had been proposed as a potential ant-viral drug target (Kwong et al. 2005). However, its positive role in interferon induction suggests that DDX3 also has an anti-viral effect. In addition, DDX3 seems to be involved in cell cycle regulation and cell growth control, and therefore we believe that a detailed investigation of DDX3 is required to fully understand and reconcile its diverse cellular functions before informed strategies for its therapeutic manipulation can be designed.
Funding:
- HRB (postdoctoral fellowship)
- NUIM start-up funding
- The Combat Diseases of Poverty Consortium
Personnel:
Postdoctoral
- Li Li Gu
- Yvette Hoehn
Postgraduate
- Ruth Brennan
- Anthony Fullam
Recent publications:
Poxvirus K7 protein adopts a Bcl-2 fold: Biochemical mapping of its interactions with human DEAD-box RNA helicase DDX3
Kalverda AP, Thompson GS, Vogel A, Schröder M, Bowie AG, Khan AR and Homans SW
J Mol Biol. 2008 Sep 27. [Epub ahead of print]
Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKe-mediated IRF activation.
Schröder M, Baran M and Bowie AG
EMBO J. 2008 Aug 6;27(15):2147-57. Epub 2008 Jul 17.
An arms race: Innate antiviral immune responses and counteracting viral strategies
Schröder M and Bowie AG
Biochem Soc Trans. 2007 Dec;35(Pt 6):1512-4.
The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like
receptor signalling
Carty M, Goodbody R, Schröder M, Stack J, Moynagh PN and Bowie AG
Nat Immunol. 2006 Oct;7(10):1074-81. Epub 2006 Sep 10.
TLR3 in anti-viral immunity: key player or bystander?
Schröder M and Bowie AG
Trends Immunol. 2005 Sep;26(9):462-8
Vaccinia Virus protein A52R activates p38 mitogen-activated protein kinase and potentiates lipopolysaccharide-induced interleukin-10
Maloney G, Schröder M, Bowie AG
J Biol Chem. 2005 Sep 2;280(35):30838-44. Epub 2005 Jul 5
Vaccinia Virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence
Stack J, Haga IR, Schröder M, Bartlett NW, Maloney G, Reading PC, Fitzgerald KA, Smith GL, Bowie AG
J Exp Med. 2005 Mar 21;201(6):1007-18. Epub 2005 Mar 14