May 2014 Lab-of-the-month - Rick Maizels
Continuing our series of featured labs from Edinburgh Infectious Diseases the Lab of the month for May is that of Rick Maizels.
Rick is the current director of Edinburgh Infectious Diseases, and also Professor of Zoology in the Institute of Immunology and Infection Research, based in the Ashworth Laboratories at Kings Buildings. His lab is working to understand the complex molecular mechanisms that allow muticellular parasites to evade the sophisticated mammalian immune system, with a particular focus on helminthic worms.
Rick started his career as an undergraduate student at UCL and carried out his PhD at the National Institute of Medical Resarch in London. He then spent a few post-doctoral years in California before returning to London as an independent researcher. He moved his growing lab to Edinburgh in 1995 and recently has been variously at the helm of the Institute of Immunology and Infection Research, Director of the Wellcome Trust-supported Centre for Immunity, Infection and Evolution, and is now the Director of Edinburgh Infectious Diseases.
L to R: Rick Maizels; recent lab portrait; Ashworth labs; fine picture of helminthic worm H. polygyrus
As well as guiding his extremely active research group Rick also organises the annual Molecular and Cellular Biology of Helminth Parasites conferences which take place each year in September on the greek island of Hydra. For details about this year's conference please click here.
Parasites and the immune system
The Maizels lab is a multidisciplinary group of immunologists, parasitologists and molecular biologists who study some of the most complex organisms to invade the human body – multicellular helminths – including some which cause widespread tropical diseases and which display fascinating biological properties. The organisms of particular interest in the lab are nematode parasites because they display remarkable biological properties and are tractable at a molecular and cellular level. For example, the filarial nematode is transmitted by mosquito and infects 120 million people in developing countries.
Parasites can live in their hosts for 5 years or more, effectively acting as successful tissue transplants. The lab hopes to understand how these organisms achieve this feat, and thereby indentify new pathways to control both parasites and the immune system. In particular, the lab is testing the hypothesis that helminth parasites exploit the body's own safety mechanisms which have evolved to minimise the risk of autoimmunity. For example, regulatory T cells naturally arise to limit autoreactivity in the immune system, but are also associated with chronic helminth infection. The expansion of regulatory T cell populations may underlie the epidemiological association between infection and reduced levels of allergy.
The labs has three main areas of research in parasite biology
One of the main intersts of the lab is in proteins and glycoconjugates secreted by live parasites which are likely to interact with the host (see our review by Hewitson et al., 2009 Mol Biochem Parasitol 167: 1-11).
Nematode parasites have sizeable genomes, at 1-3 x 109 bp which is up to 10% of the size of their mammalian hosts. Several of the major organisms are now the subject of full genome sequencing, and the lab is collaborating with the Wellcome Trust Sanger Institute in their genome projects on Nippostrongylus brasiliensis and Echinococcus granulosus, and conducting in-house transcriptomic studies of Heligmosomoides polygyrus.
Further details on molecules which we are studying as candidate "immune evasion" mediators by viewing "Immune Evasion Genes from Parasitic Nematodes".
Parasites which live in mammalian hosts for long periods are successful xenografts, and must survive by altering the host cellular immune response to attenuate or ablate attack. Certainly, parasites have evolved a web of mechanisms for diverting host immune responses. The lab is dissecting this system by analysing the status, phenotype and specificity of host immune cell populations. They are particularly interested in two dominant, but competing, host cell populations: the Th2 and Treg subsets.
Th2 responses are virtually universal among helminth parasite infections. Currently, they are analysing the initiation of Th2 responses in vivo, alongside identification of the parasite molecules which induce this reaction.
The Maizels lab has also defined Treg populations in chronic helminth infection (see "Regulatory T cells in Parasite Infection"), and are testing the hypothesis that these cells are responsible for the suppression of key T cell functions such as antigen-specific proliferation and secretion of pro-inflammatory cytokines.
There is now little doubt that down-regulation of the immune system during helminth infections can spill over to modulate other responses, including allergies, autoimmune diseases, other infections and even responsiveness to vaccination. Allergies and helminth infections share a Th2-dominated immune response, and yet allergic disease is lowest in developing countries with high parasite prevalences. By studying the interaction between parasite infection and susceptibility to allergies, using chronic models of airway allergy, we are testing the “Hygiene Hypothesis”.
In models of animal airway allergy, the lab has found that helminth infections down-regulate inflammation, and indeed protection from allergy can be conferred by introducing secreted helminth proteins rather than live infection. This result is being pursued with a view to developing new therapies for allergy. The same infections also delay and mitigate autoimmune pathology such as experimental autoimmune encephalitis, a model for human multiple sclerosis. Again, the possibility of applying the natural suppressive effects of parasites (and their products) to critical disease conditions is one the lab is pursuing.
Lab members - happily located on the 3rd floor of Ash2, but shortly moving along the corridor to 3rd floor Ash3
- Henry McSorley
- Works on helminth suppression of allergies and recently awarded an Asthma UK Senior Postdoctural Development Award (2013-2016).
- Danielle Smyth
- Studies helminth molecules protecting against inflammatory bowel disease.
Research Assistants and Technicians
- Janice Murray, joined in 1996
- Manages laboratory business and works on cystatins and venom allergen-like (VAL) proteins from filarial parasites.
- Yvonne Harcus, joined in 1997
- Runs parasite life cycles, and conducts proteomics analyses on Brugia, Nippostrongylus and Toxocara. Also works on novel secreted proteins from Heligmosomoides polygyrus.
- Angela Reid, joined in 2005
- Provides a wide range of essential laboratory support services.
- Elaine Robertson, joined in 2011
- BSc from Edinburgh Napier University.
- Stephanie Ryan, Joined in September 2011.
- Works on analysis of aprasite homologues of clinically significant environmental and food allergens.
- Chris Johnston, joined 2012
- Andrea Kemter, joined 2012
- Works on modulation of dendritic cells by helminth products.
- Gillian Coakley, joined 2012
- Studies secreted helminth microRNAs and their effects on host cells (Co-supervised with Dr Amy Buck).
- Xuhang Wu, joined 2013
- Works on functional analyses of abundant proteins in Brugia Malayi.
The lab has recently received a number of awards:
- During the recent 1st European Meeting for Young Researchers on soil-transmitted Helminths: “Host-helminth Interactions from a Global Health Perspective” (Jongny, Switzerland; March 2014), no fewer than three lab members returned with prizes:
- Best Poster Presentation Award: Janice Murray
- Best Oral Presentation Award: Gillian Coakley
- Best Combined (Oral & Poster) Presentation Award: Chris Johnston;
- Chris Johnston was also recognised by the Association of Surgeons in Training, being awarded the prestigious ASiT Medal for Transplantation Research for the presentation: "A Role for Helminths in Achieving Immunological Tolerance" (March 2014);
- Post-doctoral fellow Henry McSorley has been appointed as a University of Edinburgh Chancellor's Fellow by the College of Medicine and Veterinary Medicine (April 2014).
Many congratulations to all!
Links to recent publications
- Maizels RM, McSorley HJ, Smyth DJ. Clin Exp Immunol. 2014 Apr 18. doi: 10.1111/cei.12353.
- Hewitson JP, Maizels RM. Expert Rev Vaccines. 2014 Apr;13(4):473-87.
- Hewitson JP, Rückerl D, Harcus Y, Murray J, Webb LM, Babayan SA, Allen JE, Kurniawan A, Maizels RM. PLoS Pathog. 2014 Feb 27;10(2):e1003930.
- Filbey KJ, Grainger JR, Smith KA, Boon L, van Rooijen N, Harcus Y, Jenkins S, Hewitson JP, Maizels RM. Immunol Cell Biol. 2014 Feb 4. doi: 10.1038/icb.2013.109.
- Smith KA, Maizels RM. Eur J Immunol. 2014; 44(1):150-61.
- Johnston CJ, McSorley HJ, Anderton SM, Wigmore SJ, Maizels RM. Transplantation. 2014 Jan 27;97(2):127-32.
- Hewitson JP, Ivens AC, Harcus Y, Filbey KJ, McSorley HJ, Murray J, Bridgett S, Ashford D, Dowle AA, Maizels RM. PLoS Pathog. 2013 Aug;9(8):e1003492.
To read more about the Maizels lab please visit their webpages at http://maizelsgroup.biology.ed.ac.uk/research-rick-maizels-lab
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