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Are you an early career researcher looking for a challenge? Do you have a background in Cancer Biology, Immunology or Virology?  Can you provide technical support to research projects? Do you want to further your career in one of the UK’s leading research-intensive Universities?

A new paradigm in virus-mediated immunotherapy for liver cancer.

University fo Leeds are seeking a research technician to work on a new approach to liver cancer immunotherapy in the laboratory of Dr Stephen Griffin. You will use a range of molecular immunology and cell biology approaches to study therapeutic immune responses to liver cancer, driven by a new virus-based immunotherapy.

Advanced liver cancer is the fastest-growing cause of cancer-related deaths worldwide and current targeted therapy extends life expectancy by only a matter of months. However, harnessing the power of our own immune systems – immunotherapy - is showing increasing promise for the treatment of otherwise incurable malignancies. Cancer-killing, or “Oncolytic” viruses are increasingly used to evoke therapeutic immune responses in cancer patients, an example of which is now commonly used to treat malignant melanoma in the skin. They have discovered that modifying a particular oncolytic virus to prevent its ability to replicate dramatically improves therapy in preclinical models of liver cancer, as well as promoting synergy with the targeted cancer drug, Sorafenib.

This four-year project, funded by the Medical Research Council (MRC), seeks to both optimise and understand how the modified virus co-operates with Sorafenib to evoke immune responses against malignant hepatocytes. In particular, it will explore the immunological mechanisms that distinguish effective therapy within both primary human liver tissue and preclinical models of liver cancer. We will employ a range of techniques spanning functional immunology, molecular virology and cell biology, histochemical and immunofluorescence tissue analysis, as well as next generation transcriptomics designed to discriminate immunological phenotypes. The objective will be to achieve comprehensive understanding of the fundamental processes by which host immune responses target liver cancers, as well as providing the foundation for future clinical studies exploring this novel therapeutic approach.

You will have a background in cancer/cell biology/immunology/virology, and an interest in applying that expertise to the study of tumour immunotherapy. You will join a team of researchers focussing on the mechanisms of virus-host interactions in the cancer field.

Role Description

Department

Immunology is a primary research focus within the York Biomedical Research Institute. Their work aims to reveal the molecular mechanisms underpinning immunity and immunopathology during complex infectious and non-communicable inflammatory diseases. In this context, leishmaniasis is a globally important parasitic disease with over 1M new cases each year across 98 countries. The York Biomedical Research Institute boasts one of the largest groups of researchers working on leishmaniasis in academia, with partnerships in >20 countries. Their work on leishmaniasis spans the whole spectrum from mechanistic immunology, parasite biology to human challenge and vaccination trials. This immunology post is funded by a MRC-FAPESP Joint Centre Partnership award between the University of York and the University of Sao Paulo and is funded for two years.

Role

They are seeking to appoint a postdoctoral scientist with a strong interest in mechanistic immunology to carry out research on the microenvironmental control of myeloid cell function, using single-cell transcriptomics and multiplex spatial profiling (e.g. GeoMx Digital Spatial Profiling). You will have the opportunity to work in multidisciplinary team. You will conduct an independent research project using tissue samples derived from clinical cohorts in endemic countries and from animal models of infection, whilst also working with a larger team. You will analyse and interpret research data to address timely questions in myeloid biology and identify future research directions. You will write up research results, and disseminate them through publications, lab meetings, seminar and conference presentations and public engagement activities.

Skills, Experience & Qualification needed

You will have a PhD in immunology or a related discipline and an interest in discovering molecular mechanisms driving immunity to infection. You will have knowledge of myeloid cell biology including research around heterogeneity and its relationship to function. You will have research expertise in cellular and or molecular immunology, specialist IT knowledge, knowledge of flow cytometry, imaging and or immunohistochemistry and a broad understanding of immunology/immunity to infectious disease. Knowledge of single cell profiling technologies and pipelines is desirable but not essential.

You will have an excellent track record of research evidenced through publications. You should be highly motivated, and able to engage with scientists, clinicians and other research staff to deliver your research. A willingness to travel to overseas clinical sites to assist in sample collection is essential.

A Postdoctoral Scientist position is available in Dr Jan Rehwinkel’s group in the MRC Human Immunology Unit in Oxford. You will play a key role in studies dissecting the role of the innate immune system in cancer. The group investigates how nucleic acids that are produced during infection with a variety of viral pathogens or in autoinflammatory diseases and cancer trigger immune receptors, focussing on innate sensors that survey the cytoplasm.

The project will follow on from our interest in SAMHD1. This interesting protein plays roles in virus infection, autoimmunity and cancer, and the latter will be dissected in this project. This work will involve in vivo models, as well as in vitro techniques including genome editing, molecular biology and cell culture. This work will be funded by the CRUK-LifeArc-Ono Immunooncology Alliance.

It is essential hat applicants have a PhD or anticipate completing a PhD in the near future. You will need to demonstrate a flair for original research from your proven track record and previous experience in innate immunology, cancer, or a related area. Previous experience with in vivo cancer models is desirable. You will be required to display flexibility, commitment and a willingness to innovate, delivered via excellent communication skills. You must have the ability to work efficiently as part of a team as well as independently. Additionally, you will be prepared to take initiative to offer help and advice to colleagues and liaise effectively with the Group Leader

Recruitment of leukocytes from the circulation to underlying tissues is a fundamental process that is critical to development and fighting infection. However, when this process goes wrong it is central to inflammatory diseases such as rheumatoid arthritis as well as atherosclerosis and cancer. 

Chemokines are the key regulators of leukocyte recruitment; they are presented on the endothelial surface where they bind to their receptors on circulating leukocytes. Chemokine interactions with their receptors lead to signalling events that enable movement of leukocytes from the circulation through the endothelium and into underlying tissues. The chemokine system collaborates with the extracellular matrix to drive leukocyte recruitment, but we are yet to successfully target chemokines during inflammatory disease.

This project is focused on understanding how the glycocalyx, an extracellular matrix barrier that lines blood vessels, collaborates with chemokines to regulate leukocyte recruitment. Manchester have demonstrated that certain chemokines may function by directly modulating the glycocalyx barrier and not via the classical mechanism of signalling through chemokine receptors. They have also demonstrated that the biochemistry of the glycocalyx is tuned to produce interaction with, and localisation of, specific chemokines. This will build upon a series of recent papers demonstrating that the chemokine system is built upon specificity and not redundancy.

This project will utilise cutting edge multi-photon imaging in vivo to directly study the glycocalyx and dissect its role in regulating leukocyte recruitment at rest and during inflammation. A truly multi-disciplinary approach is taken within the newly established Dyer lab, incorporating biophysics, biochemistry and in vivo immunology. Ultimately this will lead to development of novel therapeutics to ameliorate inflammatory disease and cancer.

You will be responsible for driving forward an exciting and innovative package of work to directly image the glycocalyx and determine how it is regulated during inflammation to facilitate leukocyte recruitment. 

Successful candidates may be subject to pre-employment screening carried out on our behalf by a third party. The offer of employment will be dependent on the successful candidate passing that screening. Whilst you will be required to provide express consent at a later stage, by continuing with your application now you acknowledge that you are aware that such screening will take place, and agree to take part in the process.