Understanding the heterogeneity of diseased tissue using state of the art omics technology for the prevention and treatment of disease

Lead Research Organisation: University of Brighton
Department Name: Sch of Applied Sciences (SAS)

Abstract

Effective treatment of disease requires early and precise diagnosis and an understanding of how the disease has changed the functioning of the tissue. The work of the Centre for Stress and Age-Related Disease and the Centre for Regenerative Medicine and Devices based at the University of Brighton, has focused on developing a range of new treatments and early diagnostics for diseases that are prevalent in older people. Our current funded work explores a range of conditions including osteoarthritis, incontinence, cancer, neurogenerative diseases and diabetic leg ulcers, conditions that have a major impact on the quality of life and life expectancy of older people. Current treatment for many of these conditions is limited and aims to manage symptoms rather than to slow down or halt disease progression. Early diagnosis and the prevention and progression of disease is now a research priority for many age-related conditions, alongside the development of novel medicines/devices that can more effectively treat the conditions. Diseased tissues are made up of a range of different cell types. Much of the current work published has explored how disease alters the expression of genes and proteins in the tissue. However, this work fails to identify which cell types are affected. This information could provide us with greater insight into the origins of the disease. In order to facilitate these new discoveries, researchers at the University of Brighton, together with the Brighton and Sussex Medical School and the University of Sussex are requesting funds to purchase a laser microdissection microscope. This instrument will be utilised to dissect out diseased tissue, single cells or groups of homogenous cells from complex heterogenous tissues or from tissues in contact with biomedical devices (novel wound dressings), allowing their properties to be compared to healthy controls. The data generated will be used in three ways. First, the data will provide us with a set of biomarkers of accelerated tissue ageing or of disease that with further research would contribute to early disease diagnosis and be predictive of disease in the healthy. Together this would provide us with the opportunity to prevent disease initiation and/or progression and improve prognosis. Second, it will allow the development of personalised medicine. Third, it will allow the development of novel wound dressings that have the ability to monitor healing at the same time as facilitating the healing process. Fourth, it will enhance our understanding of antimicrobial resistance.
Our links with the local medical school has already facilitated some of our work to move from pre-clinical models to clinical samples and this joint application and our involvement in the development of a local health research partnership will further strengthen these links with the local NHS hospitals Trust and facilitate more of our work reaching the clinic.
In summary, the successful completion of this body of research will improve our understanding of a range of diseases as well as their regenerative properties and will lead to earlier more precise diagnosis of disease, personalised medicine and the development of novel treatment strategies.

Technical Summary

Effective treatment of disease requires early and precise diagnosis and an understanding of the pathophysiology of disease. Our work at the University of Brighton, alongside colleagues at the Brighton and Sussex Medical School and the University of Sussex, has focused on developing a range of novel treatments and early diagnostics for diseases of older people. Our current funded work explores a range of conditions including osteoarthritis, constipation/incontinence, a range of cancers, neurodegenerative diseases and diabetic leg ulcers. These conditions are costly to manage, impact massively on quality of life of the patient and can impact on life expectancy. The development of effective treatment strategies would be facilitated by earlier and more precise diagnosis, and a more in depth understanding of the pathophysiology of the condition. Tissues are heterogenous in terms of cell type, and in disease healthy and diseased cells may co-exist in a single tissue. Additionally, some cancers are not a single disease but instead a multiplicity of distinct malignancies that share a common anatomical site. Understanding the cell types that are affected by disease will improve our understanding of the condition and lead to the development of novel diagnostics, treatments and personalised medicine strategies. To aid these goals we request a laser microdissection microscope to enable us to dissect out diseased tissue, single cells or groups of homogenous cells from complex heterogenous tissues or from tissues in contact with biomedical devices, allowing the expression of genes and proteins to be compared to healthy controls and across the stages of disease. This work will lead to the development of miRNA, neurochemical and imaging biomarkers that can be used for the early diagnosis of disease, identify mutational and translational features for improved prognosis and the development of innovative treatments, including novel drug therapy and theranostic wound dressings.

Publications

10 25 50