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2016 Research Grants

Hunting for human infectious agents in Genomics England’s 100,000 genome project

Amount Funded: 
£70,427 (36 months starting 1 April 2017)

Research Organisation:
Norwich Medical School, UEA

Grant Applicants: 
Dr Daniel Brewer
Senior Lecturer
Prof Colin Cooper
Chair of Cancer Genetics

Lay Summary of Research: 
Infectious agents, such as bacteria and viruses, are involved in the development of a variety of human cancers such as cervical, liver, stomach and bladder cancer. We hypothesise that other infectious agents are directly linked to cancer development, but as yet remain undefined. We are now in an era where the genetic code (sequence) of any sample can be read relatively inexpensively compared to when the sequencing of the original human genome was completed. When a tissue sample from a cancer patient is sequenced, material from both human cells and any infectious agents present will be read. This has led us to develop an analytic pipeline, named SEPATH, to identify infectious agents present in cancer samples from sequence data. Genomics England’s 100,000 Genome project is a large-scale initiative, backed by the UK government, to sequence samples from 40,000 cancer patients from a range of different cancer types. Through a competitive process we have been awarded access to apply SEPATH to this data (no funds awarded). We have applied for funds for a PhD student to carry out this work and take advantage of this amazing opportunity to investigate new pathogens linked to cancer.

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Development of a multi flor-omic platform to functionally interrogate the calcium signalling pathway in colorectal tumours: implications for cancer prevention and chemotherapy

Amount Funded: 
£82,802 (12 months starting 1 July 2017)

Research Organisation:
School of Biological Sciences, UEA

Grant Applicants: 
Dr Mark Williams
Senior Lecturer
Dr Iain Macaulay
Group Leader


Lay Summary of Research: 
Colorectal cancer (CRC) is the fourth most common form of cancer and the second leading cause of cancer-related death in the Western world; each year over 41,000 people are diagnosed in the UK (1 person every 15 mins), leading to approximately 16,000 deaths per annum. Notwithstanding clinical screening programmes and complementary advances in surgery, chemotherapy and radiation treatment, just over half of these individuals live for more than 10 years (Cancer Research UK). In recent years, significant progress has been made in understanding the origins of colon cancer and the processes that control its growth. It has also become clear that the genetic make-up of colon cancer can differ between individuals which helps explain why chemotherapy is not ‘one size fits all’.   This project will use state-of-the-art techniques to grow colorectal tumours in the laboratory so as to understand how the genetic make-up of each tumour confers the massive growth and survival potential that are the hallmarks of cancer.  Armed with this information, it is hoped that new chemotherapies can be developed that are tailored to the individual. 

An exciting new collaboration has been formed between a gastrointestinal physiologist (Mark Williams, UEA) and a genome biologist (Iain Macaulay, Earlham Institute). Essentially, this powerful combination of expertise will be able to detect defects in the genes of colon cancer cells and comprehend how this translates into tumour formation and growth. Recent observations suggest that calcium signals, which act like Morse code, are corrupted in genetically altered cancer cells and end up sending evil messages to grow, invade and disrupt surrounding normal tissues in the intestine and beyond.  A major aim of this project is to crack the ‘calcium code for colon cancer’ and subvert these sinister signals by intercepting them with novel drugs that will make these hostile cells more susceptible to chemotherapy.


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Preventing prostate cancer progression through depleting ATP in the tumour microenvironment by dietary intervention

Amount Funded: 
£119,987 (48 months starting 1 Jan 2017)

Research Organisation:
Institute of Food Research, Norwich

Grant Applicants: 
Prof Richard Mithen
Programme Leader
Dr Maria Traka
Senior Scientist


Lay Summary of Research: 
There is strong evidence that men who eat diets rich in cruciferous vegetables, such as broccoli, have reduced risk of aggressive prostate cancer. However, only a relatively few men eat sufficient amounts to have a significantly reduced risk. A long-term project at the Norwich Research Park has developed special broccoli varieties with possible enhanced levels of anti-cancer activity. We have now used these novel broccoli varieties in a year-long diet study with men who have a diagnosis of low and intermediate risk of prostate cancer. We tested prostate biopsy samples from these men after the diet study. We found that in many of them the cancer had either not progressed or had decreased, and that these changes were, unexpectedly, linked with an increase of sulphate and decrease of ATP – which is the main energy source in human tissue and is important for cancer cells to grow. In the proposed project we wish to understand how broccoli causes these changes. This new understanding will help us improve our broccoli varieties and give more information on how often and in which way our special broccoli should be eaten to boost cancer protective benefits.

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Exploiting imaging mass spectrometry to investigate excision margins in melanoma: a pilot study

Amount Funded: 
£42,543 (12 months starting 1 Dec 2016)

Research Organisation:
School of Biological Sciences, UEA and Norfolk and Norwich University Hospital

Grant Applicants: 
Dr Jelena Gavrilovic
Senior Lecturer (Cell Biology)
Mr Marc Moncrieff
Consultant Plastic and Reconstructive Surgeon (NNUH)


Lay Summary of Research: 
Melanoma is a type of cancer that most commonly develops in the pigmented cells in the skin, often associated with following UV exposure from sunlight. It is the fifth most common cancer in the UK and effects a much younger population than other types of cancer. Treatment for melanoma involves the removal of the primary tumour in order to stop it spreading to other parts of the body.  Because this type of cancer is usually pigmented it is possible to see its outline on the surface of the skin. As with any cancer it is essential that all cancerous cells are removed so, in addition to the pigmented cells an area of “normal” tissue surrounding the melanoma is also removed. It is important to take all the cancer away but it is uncertain how much of the “normal” tissue needs to be removed and procedures differ widely across the world. Removing a lot of the surrounding tissue can lead to less desirable consequences including pain and disfigurement, depending on the location of the melanoma. The Norfolk and Norwich University Hospital is leading a big clinical trial (in the Norwich and around the world) to try to establish how much skin from around the melanoma needs to be removed to prevent recurrence of the cancer.  The tissue that is removed around the melanoma is studied under a microscope by hospital pathologists to make sure no cancerous cells are left but as we understand more about cancer we know that molecules in the tissue, which are invisible under the microscope, are also important in helping cancer spread and recur.  We will be using a new and very sensitive method to look for the presence of pro-cancerous molecules in the tissue surrounding the melanoma.  We will be looking in regions 1cm and 2cm away from the melanoma to see if we can identify the smallest amount of tissue that can be removed to stop the cancer returning. We may also be able to use the new findings to plan other ways to treat melanomas which have started to spread round the body.

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13C- and 2H-derived Carbohydrate Based Hyperpolarised MRI Agents For Tumour Imaging
 

Amount Funded: 
£115,721 (36 months starting Sept 2017)

Research Organisation:
School of Chemistry, UEA

Grant Applicants: 
Dr Sean Bew
Senior Lecturer
Prof Kevin Brindle
Professor (Cambridge University)


Lay Summary of Research: 
The earlier cancer is detected the more quickly and more effectively it can be treated. One technique currently widely employed in the clinic is positron emission tomography or PET. In essence PET comprises two parts: the first is the administration of a ‘chemical signaller’ called FDG, which is taken up in relatively large quantities by cancer cells. The other part is a detector that locates the FDG in the body and thus shows where tumour cells are present. This technique works well, but it is not ideal. The FDG is radioactive, emitting very high energy radiation that is itself potentially harmful. Ideally a safer method to detect cancer is required. Such a protocol may also help with long-term cancer treatment and the development of new anti-cancer drugs.

Our research aims to generate a safer method for detecting cancer cells using slightly modified and non-radioactive derivatives of glucose and fructose. These are used by your body to generate energy, and at the doses we will use have no harmful biological effects. Furthermore, the technique used to detect these labelled sugars, MRI, is already widely available in the vast majority of hospitals and is also regarded as very safe.

How does the process work? One important aspect of a cancer cell is that it requires lots of energy. This is generated in a process called metabolism. Metabolism allows the cancer cell to keep growing by acquiring the energy and building blocks it needs from sugars such as glucose. Because this metabolism is substantially higher in cancer cells than in surrounding normal cells we can detect where the tumour cells are by monitoring increased metabolism.  We propose to substitute the carbon atoms of glucose with a special form of carbon called 13C and incorporate special forms of hydrogen called deuterium, which have no tangible effect on glucose uptake by the cancer cell but they do allow a special technique, called hyperpolarisation, to be used to detect them (using the MRI machine). Our research will generate a series of sugars with 13C and deuterium at various locations on the sugars. Because the locations are different we need to determine which location is preferable at sending back to the MRI machine the strongest ‘signal’ when the sugar is taken up and metabolised by the cancer cell. Unlike FDG-PET, which uses strong radiation, an advantage of our technique is that no ionising radiation is used and so it can be used repeatedly with no detrimental effects, allowing more frequent monitoring of any effect an anticancer drug is having on a tumour. Our technique has the potential to speed up cancer diagnosis, and to make treatment more personalised, safer and accurate.