Cell Signalling
Cell signalling is the process by which cells and molecules communicate information to each other. This process evokes a functional response. These mechanisms allow cells to respond to both extra and intracellular signals. This underpins many areas of biology.
Disruption of these pathways can cause or contribute to the pathology of many human diseases. It also causes impact on the pathobiology of infectious agents such as:
- bacteria
- viruses
- fungi
Targeting these pathways forms the basis of many current and future clinical therapies.
Our multi-disciplinary approach of this theme will encompass fundamental, applied and translational research. Our focus is on dissecting and understanding the molecular basis of cell signalling in normal cellular function. We're investigating this in disease and in model and pathogenic organisms.
We aim to exploit this knowledge to help develop or improve new and existing therapies.
We investigate the pathways leading to cancer development and resistance to current therapies. Our aim is to improve current treatments and identify targets for new anti-cancer drugs. Our specific interests include:
- The function of the NF-kB pathway in cancer development and therapy resistance. Lead: Neil Perkins
- Exploiting and understanding DNA damage signalling in cancer cells. Leads: Neil Perkins, Ruchi Shukla, John Lunec
- Oncogenic and tumour suppressor signalling networks. Leads: John Lunec, Neil Perkins
- The genetic and epigenetic changes involved cancer initiation and progression. Lead: Ruchi Shukla
- Identifying new therapeutic targets for the treatment of prostate cancer. Lead: Kelly Coffey
- The role of post-translational modification enzymes. Including protein kinases, in the androgen receptor NF-kB signalling pathways.
Leads: Kelly Coffey, Neil Perkins - The role of age-related mitochondrial defects in the development of colon cancer. Lead: Laura Greaves
- The role of Innate Lymphoid Cells in melanoma and cutaneous squamous cell carcinoma tumour. Lead: Shoba Amarnath
- The role of ribotoxic stress in cancer cell signalling. Lead: Nick Watkins
- Kinase signalling mechanisms that underpin cell division. Lead: Jonathan Higgins
- Autophagy in cutaneous skin cancer and oropharyngeal squamous cell carcinoma development and metastasis. Harnessing this process for clinical benefit, including biomarker development and therapeutic strategies. Lead: Penny Lovat
- The immune microenvironment of liver cancer, with a particular focus on neutrophils. As well as the chemokine receptor CXCR2 as a new immunotherapeutic cancer target. Lead: Derek Mann
We are seeking a mechanistic understanding of how perturbation of cell signalling contributes to ageing and age-related disease. This has the potential to improve the quality of life (the ‘healthspan’) for millions of people.
Our aim is to understand these fundamental processes in both healthy and diseased tissue. This will lead to ways we can protect our cells from age-related decline. Our specific interests include:
- Understanding the essential catabolic process of autophagy. Promotes the removal of damaged and potentially damaging cellular components. Including protein aggregates and dysfunctional mitochondria. Lead: Viktor Korolchuk
- The role of age-related mitochondrial defects in metabolism and cancer. Lead: Laura Greaves
The immune system is tightly regulated by multiple signalling pathways. These determine immune activation versus immune tolerance. Receptors known as co-receptors play a vital role in driving immune cell activation and/or inhibition.
Understanding the role of these receptors and the signalling pathways they regulate is critical for the effective use of new immunotherapies for cancer and other diseases. We are interested in:
- The role of the CTLA4 and PD-1 co-receptors as potent checkpoints. How these can be targeted for boosting immune responses in cancer.
Lead: Shoba Amarnath - Investigating the innate immune response using state-of-the-art proteomics. Especially cell signalling mediated by macrophage phagosomes.
Lead: Matthias Trost - Identifying cell-type specific roles for ROS-signalling mechanisms in the innate immune defence against pathogens. Using elegans as a multicellular model organism. Lead: Elizabeth Veal
- The role of fibroblast plasticity in driving/resolving inflammation and fibrosis in the lung. Lead: Lee Borthwick
- Molecular control of inflammation and fibrosis in multiple tissues: liver, kidney, lung, heart, joints. Focussing on transcription factors and epigenetic regulators. Lead: Derek Mann
It is critical to understand how cells respond to stress during normal homeostasis and ageing. Failure to protect against the damage caused by cell stress is implicated in many diseases. These include: cancer, heart disease and diabetes.
Exposure to sunlight, immune cell attack and aerobic metabolism generate highly toxic chemicals known as 'reactive oxygen species (ROS)'. Leading to cell damage and ultimately disease. Research projects investigating cell stress and its role in disease include:
- Investigate ROS-sensing and signalling mechanisms in genetically amenable model eukaryotes. The fission yeast Schizosaccharomyces pombe and the nematode worm Caenorhabditis elegans. Lead: Elizabeth Veal
- Investigating the molecular mechanisms that activate autophagy. During localised oxidative stress and as a stress-response pathway.
Lead: Viktor Korolchuk - Control of ribosome biogenesis in normal cells and following cell stress. The nucleolus, the site of ribosome synthesis, is a major stress sensor in the cell. It becomes disrupted upon DNA damage, leading to activation of the tumour suppressor p53. Lead: Nick Watkins
Our researchers both develop and use a wide range of cutting edge technologies. These include:
- Developing and establishing proteomics techniques to answer important biological questions. Lead: Matthias Trost
- Using precision cut slices (PCS) to develop better laboratory models of fibrosis. Leads: Lee Borthwick, Derek Mann
- Building novel microscopes to develop new single-molecule fluorescence microscopy techniques. Using these to image cell signalling molecules at work in living cells. Lead: Adam Wollman
- Using CRISPR/Cas9 based genome engineering to dissect the role of protein post-translational modifications and cancer mutations.
Lead: Neil Perkins - Developing new methods for dissecting kinase signalling pathways in cells. Lead: Jonathan Higgins
- In vivo experimental models of tissue damage. Lead: Derek Mann
Research Culture
We support early career researchers (ECRs) across all career stages. From PhD students to research fellows newly gaining independence. We help ECRs to:
- find a mentor
- identify fellowship funding streams
- assist with their applications and prepare for interviews
- provide confidential pastoral care.
Regular training and networking events support and develop our next generation of future leaders.
ECR Leads: Elizabeth Veal, Shoba Amarnath, Kelly Coffey.
We strive to implement university’s Equality Diversity and Inclusion policy within our theme. We encourage family-friendly flexible working patterns.
EDI Lead: Ruchi Shukla.
We are keen to develop teaching modules and undergraduate/MRes projects based on our research.
Educations Leads: Alessio Iannetti, Neil Perkins.
Research in Progress talks provide an opportunity to discuss data in an informal and supportive setting. Postgraduate students, researchers and technicians are all encouraged to take part.
Research in Progress Lead: Laura Greaves.