The Immunology, haematology and infection (IHI) theme builds on a history of internationally-leading immunology and infection research at York. Over the last decade, we've made significant contributions in the areas of neglected tropical disease, parasitology, cellular immunology and haematological malignancies.
Research within this theme ranges from fundamental insights into disease mechanisms, through to vaccine clinical trials and epidemiology.
- Experimental and population haematology
- Cellular immunology
- Structure-function analysis of pathogen molecules
- Microbiology, bacterial pathogenesis and AMR
We have integrated our strengths in experimental and population haematology, structural biology and biophysics to develop a collaborative and interdisciplinary research environment.
Experimental and population haematology
Many cancers are caused by mutations in genes that result in uncontrolled cell growth. Experimental haematology spans research into single molecules, for example, understanding the mechanisms of oncogenic driver mutations in myeloproliferative neoplasm (MPN) development (Hitchcock). MPNs are a group of blood cancers characterised by the over-production of red blood cells and/or platelets, and is the most common myeloid cancer.
A single stem cell can give rise to any of the highly specialised cell types of a given tissue whilst also having the capacity to make a new stem cell. If the process is dysregulated in some way, the over production of stem cells can lead to progression of cancer. Understanding the molecular regulators of normal blood stem cells and the clonal evolution of cancers from single cells (Kent) is contributing to our knowledge of how blood cancers such as leukaemia progress.
The Epidemiology and Cancer Statistics Group (ECSG) is a multi-disciplinary team of researchers. Major research themes include cancer epidemiology, in particular the determinants, prognosis and treatment of haematological malignancy, as well as cancer in children and young adults (Roman, Smith, Crouch). They co-established the Haematological Malignancy Research Network (HMRN) with the Haematological Malignancy Diagnostic Service (HMDS) at St. James Hospital in Leeds. The group analyses clinical samples and data as part of clinical trials spanning the entire spectrum of haematological disorders. Working in collaboration with clinical colleagues they then use the data to inform future decision making, improving diagnosis and prognosis of patients with haematological malignancies.
Projects aim to research the biology of the Leishmania parasite (Mottram, Walrad, Jeffares, Wilkinson, Wilson L), its interaction with the host (Myburgh) and novel therapies to treat leishmaniasis (Kaye). Academics also research immune response to schistosomiasis (Hewitson), drug and vaccine development for African trypanosomiasis (Mottram, Myburgh, Wright) and molecules involved in Plasmodium erythrocyte invasion (Wright).
They lead the UK:Brazil Joint Centre Partnership in Leishmaniasis (JCPiL), a global pathology network (LeishPathNet), and a project to develop a human challenge model for Leishmania (LeishChallenge), as well as contributing to a Global Network for NTDs focused on drug discovery. More details can be found at Leish@york.
Cellular immunology and infection
Research within cellular immunology covers areas including macrophage function (Kourtzelis) and the inflammasome (Boucher) adding to strengths in type II immunity (Hewitson) and long non-coding RNAs in immune cell function (Lagos, Plevin).
York contributes to the dose reduction immunobridging and safety study of two HPV Vaccines in Tanzanian girls trial (DoRIS, Lacey), sexual and reproductive health (Mason-Jones), and clinical epidemiology (Newton). IHI investigators (Kaye, Lagos, Signoret) are members of the recently-established UK Coronavirus Immunology Consortium (UK-CIC).
Structure-function analysis of pathogen molecules
Areas within the IHI theme are increasingly supported by structural biology including crystallography for the analysis of proteins that contribute to virulence and represent drug targets (Wilkinson), viral invasion, cancer and imaging/treatment of lysosomal storage diseases (Davies). Cryo-EM is used to study bacterial bioenergetics and identify new drugs for drug resistant tuberculosis (Blaza). Biophysical techniques are used to study multi-domain proteins involved in regulation and signalling in humans and human diseases (Plevin).
Recently YSBL purified and characterised the SARS-Cov-2 nucleocapsid protein (Antson) for the development of diagnostics and therapies. Mathematical modelling of the structure and assembly of viruses is also a major area of interest (Twarock).
Microbiology and bacterial pathogenesis
The success of a bacterial species depends on its ability to grow and survive in a changing and potentially hostile environment. This requires adaptation at both the single cell and population level. There is a particular interest in understanding the basic aspects of how the success of populations of bacterial pathogens is underpinned by phenotypic heterogeneity (van der Woude); eco-evolutionary dynamics of species interactions in communities (Friman). How bacterial pathogens scavenge the important host-derived molecule sialic acid (Thomas); and how a microbe interacts with biotic (host tissue/biofilm) and abiotic (surgical implants) surfaces (Baumann).
Due to an increase in bacterial resistance to antibiotics, there is an urgent need for novel ways of combating bacterial infections. Research at York covers topics such as how the human gut microbiome reacts to oral versus intravenous antibiotic treatments (Chong). Horizontal Gene Transfer (HGT), which is a fundamental and powerful process for the exchange of genes between bacteria and is a great concern if these genes encode virulence factors or antibiotic resistance (Fogg). Development of new antimicrobials (Duhme-Klair).
Biosensors are being developed to study bacteria and their susceptibility in the context of antimicrobial resistance with the aim of producing point-of-care healthcare technology devices (Patil, Krauss, Johnson).