Projects starting from April 2008 and ending April 2011
Grant Holder: Prof Batsheva Kerem
Institution: Hebrew University of Jerusalem, Israel
Grant Award: £113,135 for 3 years
Project Title: Studying ‘fragile sites’ in our genes
The way that cells grow, divide and die is normally tightly controlled by certain genes. Cancer is caused by changes in these genes, for example some genes can break into pieces at certain points known as fragile sites. These pieces can move around and join up with other genes. Cancer cells are known to do this at a much higher rate than normal cells - this may be involved in the cause of cancer or the way that it progresses. Scientists have also found that, when cells copy their genes, in order to make new cells, the copying process can be slowed down at these fragile sites. Professor Kerem believes that these fragile sites are difficult to copy and, when the copying process stops at one of them, it results in the chromosome breaking at that point. She is now analyzing the structure of these fragile sites to find out why they are difficult to copy and how this is related to the way they break more frequently in cancer cells.
Grant Holder: Dr Jonathan Sleeman
Institution: University of Karlsruhe, Germany
Grant Award: £105,300 for 3 years
Project Title: How cancers can spread?
Proteins inside cells can control processes such as how the cells grow and divide. Three proteins called ASAP1, h-prune and nm23H1 have been found at increased levels in cancer cells with the highest levels found in the more advanced stage cancers. The increased level of these three proteins in cancer cells increases the cells ability to spread around the body, making successful treatment more difficult. Dr Sleeman and his colleagues have found that the three proteins attach to each other inside cells. With a grant from AICR they are investigating how these proteins work together and how they are involved in controlling various activities in cancer cells which make them spread around the body. This project could provide important information to help design new cancer drugs in the future.
Grant Holder: Dr Julian Sale
Institution: University of Cambridge, England
Grant Award: £130,091 for 3 years
Project Title: Why is ‘proof reading’ our DNA so important?
The important genetic information our cells use to make proteins is encoded by our DNA. When one cell divides to form two cells, it must first make an exact copy of its DNA, so that one copy can be passed to each new daughter cell. It is vitally important that cells give their offspring an exact and correct copy of their DNA. In order to ensure this happens, the cells have checking mechanisms that try to detect and correct any damaged sections of the DNA before copying starts. Dr Sale is studying a special DNA copying mechanism that deals with damaged sections of DNA that have not been repaired in time. This can be dangerous as the mistakes this mechanism makes when copying damaged sections of DNA can lead to the cells becoming cancerous. Dr Sale is now studying how and when the cells use this mechanism in response to damaged sections of DNA and how this mechanism works.
Grant Holder: Dr Ellen Zwarthoff
Institution: Erasmus University, Rotterdam, Netherlands
Grant Award: £154,173 for 3 years
Project Title: How is the MN1 protein involved in leukaemia?
Every cell in our body contains thousands of genes that act as blueprints to make the proteins required for the cells to function. Cancer is caused by changes to either the structure or activity of certain genes that control key activities within a cell. In some cancers, one gene can become fused or ‘glued’ to the end of another one, creating a hybrid gene. Dr Zwarthoff is studying a gene called MN1, which was found to form part of a fused gene (MN1-TEL) which is responsible for causing acute myeloid leukaemia. The MN1 gene produces the MN1 protein that appears to move around and switch a variety of genes on or off, but it is not yet known how it does this. With the grant from AICR, Dr Zwarthoff is analysing exactly which genes the MN1 protein controls, what other proteins are involved and how it is able to control the various other genes in the cell. She will then compare these results with what is known about how the MN1-TEL fused protein works. Taken together, this will give us a much better understanding of the way that MN1-TEL causes acute myeloid leukaemia.
Grant Holder: Professor Graeme Murray
Institution: University of Aberdeen, Scotland
Grant Award: £107,781 for 2 years
Project Title: How do proteins change depending on the stage of the bowel cancer?
Cells contain thousands of different types of protein molecules, which carry out the wide range of functions that occur inside a cell. It is known that there are small but important differences between the proteins found in normal and cancer cells. However, we do not yet know what all of these differences are. Professor Murray is using a new technology called proteomics to analyse these differences in a large collection of colorectal (bowel) cancer samples. Professor Murray has good information about the stage of each cancer, so he will look for changes in the proteins which specifically relate to the various tumour stages. Any changes identified this way will be further examined to find out if they can be used as a new way to diagnose the stage of bowel cancer.
Grant Holder: Dr Ora Bernard
Institution: University of Melbourne, Australia
Grant Award: £158,885 for 3 years
Project Title: How is the LIMK1 protein involved in allowing cancer cells to spread?
One of the biggest challenges in cancer treatment is preventing cancer cells from spreading to other parts of the body and forming secondary tumours. Cells contain thousands of different protein molecules, which control all of the cells activities. Dr Bernard is studying a protein called LIMK1, which is known to be involved in controlling cell movement. LIMK1 is found at increased levels in cancer cells which gives them the ability to move and spread around the body. Dr Bernard has found evidence that healthy cells use another protein called Rnf6 to control their levels of LIMK1. Rnf6 appears to work by causing the destruction of LIMK1. But Rnf6 is often altered in cancer cells which prevents it from working and therefore allows the LIMK1 levels to increase. Dr Bernard is now using her AICR grant to investigate the role of Rnf6 in greater detail. Finding a way to control LIMK1 levels in cancer cells could be a way to stop cancer cells from spreading around the body and improve the success of cancer treatment.
Grant Holder: Dr Charles Laughton
Institution: University of Nottingham, England
Grant Award: £124,692 for 3 years
Project Title: Hunting for chemicals to stop cancer cells multiplying
The important genetic information our cells need to make proteins is encoded by our genes. The genes themselves and packaged into long, sausage-shaped structures called chromosomes. When cells divide, they must first make an exact copy of their chromosomes, so that one copy can be passed to each daughter cell. The ends of the chromosomes are particularly sensitive to damage and so are protected by a number of special protein molecules. Disrupting this protection prevents the cell from dividing. Cancer cells are known to be particularly sensitive to this disruption. Therefore new ways to target these special proteins and stop the cells from multiplying could be used as good cancer treatments. Dr Laughton is focussing on one of these special protective proteins called POT1. If POT1 is blocked from binding to the end of the chromosome, it should prevent cell division. He is using computer-based analysis and laboratory tests to find chemicals which can block the binding of POT1 to the chromosome. These will then be tested to find out if they can stop cancer cells from multiplying. After many further tests, some of these compounds could be developed into new cancer drugs.
Grant Holder: Professor Michael Threadgill
Institution: University of Bath, England
Grant Award: £105,811 for 2 years
Project Title: Designing new drugs to fight prostate cancer
Proteins are molecules which control many processes in cells and are essential for the cells to function. The prostate gland produces a protein called Prostate Specific Antigen (PSA for short). PSA is normally only found inside the prostate but it is able to escape into the blood if there is a cancer of the prostate. PSA inside the prostate is active and can chop certain proteins into two parts. However, when PSA escapes into the blood, it becomes attached to other proteins which block its chopping ability. Professor Threadgill is trying to take advantage of the PSA-chopping mechanism as a way to target cancer drugs to the prostate. He is doing this by making a large molecule which is harmless on its own but, once in the prostate at the site where the drug is needed, PSA can cut it to release a powerful anti-cancer drug. As PSA cannot cut anything when it is outside the prostate, this technique will ensure that the drug can only work in the prostate, which should reduce side-effects for the patient. Professor Threadgill has completed most of the difficult and time-consuming task of making this large molecule with a previous grant from AICR and will now complete the work and test it out in model systems.
Grant Holder: Dr Susan Matthews
Institution: University of East Anglia, Norwich, England
Grant Award: £106,444 for 3 years
Project Title: How can we get molecules called RNA to enter into living cells?
Cancer is caused by changes or damage to either the structure or activity of certain genes that control how cells grow, divide and die. In some cancers, stopping the activity of a specific altered gene can prevent the cancer cells from multiplying, and therefore stop the cancer from growing. Recently, a new method to do exactly this was discovered: called RNAi. To make this technique work, a small molecule of RNA must get into the cell. This can be done quite easily with cells grown in the laboratory, but it is much more difficult in patients, as molecules in the blood will destroy the RNA molecules. This means the RNA molecules have to be wrapped in a chemical ‘coat’ which a) stops them being destroyed in the blood, b) allows them to enter the cancer cells and c) is not poisonous to the patient. Dr Matthews is developing a new coat for RNA, using chemicals called multicalixarenes. Initial tests have shown that they have all the right properties to make an effective new way to deliver RNAi to cancer cells in patients. However, a number of different types will need to be made and tested out before we know if they will fulfil their promise.
Grant Holder: Dr Ronit Weisman
Institution: Tel Aviv University, Israel
Grant Award: £118,500 for 3 years
Project Title: Using yeast to study communication pathways in human cancers
Cells have a complex internal system of genes and proteins. These genes and proteins are organised into pathways in which the first activates the second and that activates the third, and so on, passing the activation signal down the pathway. These pathways are very complex, with many cross-overs and branches. Several of these signalling pathways are involved in controlling how cells grow and divide and can become significantly altered in cancer cells. This allows the cells to divide in an uncontrolled manner and form a tumour. Dr Weisman is investigating how a protein called TOR affects these pathways. She is carrying out the research in yeast cells as they also have the TOR protein but are more simple than human cells making the experiments easier. Understanding more about how TOR controls cell growth and division will help us determine the crucial differences in the way that cancer cells work.
Grant Holder: Dr Linda Smit
Institution: Netherlands Cancer institute, Amsterdam, Netherlands
Grant Award: £168,654 for 3 years
Project Title: What makes cancer stem cells so unique and dangerous?
Cancers are made of cells that grow and multiply in an uncontrolled manner. There are different types of cells in breast tumours which vary in their ability to multiply and cause cancer. Only a small number of cells within the tumour are responsible for the growth and maintenance of the tumour. These cells are called cancer stem cells. These cancer stem cells are therefore particularly dangerous, especially as they often do not die when treated with the current anti-cancer drugs. New cancer drugs to target these cancer stem cells are therefore needed. There is a crucial growth control mechanism inside cells, called the Notch pathway. Dr Smit has found that this pathway is active in the breast cancer stem cells, but not the other breast cancer cells. Dr Smit is now going to analyse which other genes and proteins in these cancer stem cells are involved with the Notch pathway and how they work together to control their activities. She hopes that her findings will identify new and more effective ways to treat breast cancer stem cells in the future.
Grant Holder: Dr Wim Vermeulen
Institution: Erasmus University, Rotterdam, Netherlands
Grant Award: £166,788 for 3 years
Project Title: How is our DNA repaired after exposure to UV light from the sun or sunbeds?
Cancer can be caused by damage to the DNA inside cells. This damage is due to many things such as chemicals in cigarette smoke or UV from sunlight. Our cells have mechanisms which can detect and repair this damage to prevent diseases such as cancer from occurring. But these repair mechanisms can sometimes become faulty which allows the DNA damage to remain causing the cells to become cancerous and tumours to develop. Dr Vermeulen is studying one particular DNA repair mechanism, called Nucleotide Excision Repair or NER for short. In particular he wants to find out how the NER mechanism is put into action following exposure to UV light and which proteins are involved. Dr Vermeulen is going to study the NER mechanism in a very simple animal – a tiny worm called C. elegans which makes the experiments easier. He will then analyse the equivalent proteins in human cells to determine what role they play in NER DNA damage repair.
Grant Holder: Dr Alison Lloyd
Institution: University College London, England
Grant Award: £232,756 for 3 years
Project Title: How is the NF1 gene involved in tumours of the nervous system?
Every cell in our body contains thousands of genes that are essential for the cells to function. Often, to make a cell do something, a number of genes have to be turned on or off. Cells can become cancerous if certain genes involved in controlling how cells grow and divide are altered, resulting in them being permanently turned on or off. Neurofibromatosis is an inherited condition which can be passed on from parents to their children. Sufferers tend to develop a number of benign nerve tumours which have a strong risk of developing into more dangerous malignant cancers. The little that is known about how these cancers develop suggests that many different types of
cells found in nerves are involved and the switching-off of a gene called NF1 is a critical step in the process. To study this further, Dr Lloyd is breeding new strains of mice in which she can vary the level of activity of the NF1 gene in the different types of cells found in nerves. She will use these mice to analyse exactly how changes in
NF1 activity cause these cells to become cancerous.
Grant Holder: Professor Jonathan Weitzman
Institution: University of Paris, France
Grant Award: £141,354 for 3 years
Project Title: How can parasites cause leukaemia?
Some cancers can be caused by certain viruses or parasites and we can learn a lot about the cancer process by studying how these organisms work. For example, infection with a virus called HPV can develop into cervical cancer. The virus hijacks the cells normal growth mechanisms to change normal cells into cancer cells. Professor Weitzman is studying an unusual cancer caused by a parasite called Theileria which can infect white blood cells in cows and cause a leukaemia-like condition. His research is focused on understanding how the parasite hijacks the blood cells to cause leukaemia. By understanding how Theileria cause cancer Professor Weitzman hopes to discover new ways to reverse the process.
Grant Holder: Dr Jesus Gil
Institution: University of Cambridge, England
Grant Award: £210,206 for 3 years
Project Title: Investigating the genes involved in breast and prostate cancers
How our cells operate is controlled by our genes. Cancer is caused by changes to either the structure or activity of certain genes that control how the cells grow, divide and die. Sometimes when certain cancer causing genes are turned on, instead of making the cells divide in an uncontrolled manner and causing a tumour, they actually send the cells into a coma-like state called senescence. There appears to be a complex and poorly-understood relationship between the systems that trigger cancer and those that trigger senescence. Dr Gil is going to use a new technique called RNAi to identify the genes that control senescence in human breast and prostate cells. He will then analyse how these genes work in order to understand the mechanism that triggers senescence.
Grant Holder: Professor Lesley Rhodes
Institution: University of Manchester, England
Grant Award: £192,597 for 3 years
Project Title: How are omega fatty acids involved in UV light causing skin cancer?
Over-exposure to UV light, usually from the sun, is known to cause skin cancer. There are two ways in which it does this: by damaging the DNA in skin cells as well as reducing the activity of the immune system in the skin. It is thought that the immune system, which normally fights infections, can also attack and destroy some early cancer cells. In addition, there is evidence, from mouse studies, that certain fats called omega fatty acids can affect the rate of skin cancers caused by UV. Omega-6 fatty acids were found to increase the rate of cancer and omega-3 fatty acids to decrease the rate of cancer. They did this by reducing or increasing the activity of the immune system. Professor Rhodes is now studying the effect that taking omega-3 fatty acids has on immune reactions in human skin. She aims to determine if omega-3 could help reduce human skin cancer by stopping UV light from reducing the activity of the skin immune system.
Grant Holder: Dr Nickolai Barlev
Institution: University of Leicester, England
Grant Award: £198,296 for 3 years
Project Title: Understanding the role of Set7/9 proteins in normal and cancer cells
Cancer is a disease caused by cells growing and dividing in an uncontrolled manner, forming a tumour. Every cell contains thousands of genes. These act as blueprints to produce proteins which carry out most of the functions within the cells. Many of these genes and proteins are altered in cancer cells and therefore operate quite differently, causing the cells to grow and divide rapidly and out of control. A protein called p53, which has an extremely important role in controlling how cells grow and die, has been found to be damaged or absent in half of all human cancers. Normally, p53 appears to prevent cells from becoming cancerous. Dr Barlev has identified another protein called Set7/9 which controls the activity of p53. This finding implies that changes to Set7/9 might also make a cell cancerous. To examine this possibility, Dr Barlev is analysing how Set7/9 operates in both normal and cancer cells.
Grant Holder: Professor Golan Mohi
Institution: State University of New York, USA
Grant Award: £114,720 for 3 years
Project Title: The role of hybrid genes in leukaemia
Every cell in our body contains thousands of genes that act as blueprints to make the proteins which carry out most of the activities in the cell. Cancer is caused by changes to either the structure or activity of certain genes that control how the cell grows, divides and dies. In some cancers, one gene can become fused or ‘glued’ to the end of another one, creating a hybrid gene. Such gene fusions are found quite often in leukaemia. One of the best-studied gene fusions is between the BCR and ABL genes, which causes a common form of chronic myeloid leukaemia. Professor Mohi has discovered that another gene, called Gab2 is required for the BCR-ABL fusion gene to cause leukaemia. The Gab2 gene is also required for other gene fusions or alterations to cause leukaemia-like conditions. He is now going to analyse the role played by the Gab2 gene in these cancers.
Grant Holder: Professor Ian Stratford
Institution: University of Manchester, England
Grant Award: £180,000 for 3 years
Project Title: Designing potential anti-cancer drugs
Proteins carry out most functions within cells and they control processes such as how the cells grow and divide. The protein NQO1 is found at high levels in many types of cancer, where it appears to play an important role in the breakdown of substances in the cell. In the laboratory it has been shown that blocking the activity of NQO1 can stop pancreatic cancer cells from growing. This suggests that chemicals that block its activity may be effective drug treatments for various types of cancer. Professor Stratford is therefore making a range of chemicals designed to block the activity of NQO1 and will then test them out to determine if they could make potential anti-cancer drugs.
Grant Holder: Dr Sheila Graham
Institution: University of Glasgow, Scotland
Grant Award: £185,411 for 3 years
Project Title: How can a protein in the virus HPV allow cervical cancer to spread?
Up to 8 out of 10 people (80%) in the UK are infected with the HPV virus at some point during their lifetime and for many people, the virus causes no harm and goes away without treatment. However, HPV is the major cause of cervical cancer. This is why the national vaccination programme has recently been started: to prevent HPV infections. Research has identified one particular virus protein - called E6 - as the molecule required to make normal cervix cells become cancerous. Dr Graham has found evidence suggesting that the E6 protein has another role: causing advanced cancer cells to spread and form secondary tumours. It appears to do this by stopping the cancer cells from sticking together like healthy cells do. It is only when they stop sticking together that they can break free and spread into other tissues. Dr Graham is now analysing exactly how the E6 protein does this, which other proteins inside the cell it binds to and how this interferes with the cell-cell attachment.
Grant Holder: Professor Rene Medema
Institution: University of Utrecht, Netherlands
Grant Award: £151,626 for 3 years
Project Title: How do cells restart the copying machinery inside them?
All of the information that our cells need is coded in our genes, which are made of DNA. When a cell divides to produce two new cells, it firstly has to copy all of its DNA and then give one complete set of genes to each daughter cell. The DNA is carefully protected from damaging influences, because an incomplete or damaged set of genes can make a daughter cell malfunction - and in some cases it can lead to the cell becoming cancerous. All cells have checking mechanisms to halt cell division and repair any damage to the DNA before restarting the cell division. This prevents copying of the damaged DNA and stops it being passed on to the new cells, providing an important barrier in the formation of cancer. Professor Medema is studying the mechanism by which cell division restarts after the DNA has been damaged. He has found that the protein called Plk1 plays a key role and he will now analyse all of the other proteins that work with Plk1 to find out how the restart mechanism operates. This will provide important insights into the mechanisms that contribute to cancer formation.
Grant Holder: Dr Ruth Palmer
Institution: Umea University, Sweden
Grant Award: £171,540 for 3 years
Project Title: Using fruit flies to study lymphomas
Every cell in our body contains thousands of genes that act as blueprints to make the proteins required for the cells to function. Cancer is caused by changes to either the structure or activity of certain genes that control how the cells grow, divide and die. In some cancers, one gene can become fused or ‘glued’ to the end of another one, creating a hybrid gene. Dr Palmer is studying a gene called ALK, which was discovered about 10 years ago, fused to other genes in many cases of non-Hodgkins lymphoma and anaplastic large-cell lymphoma. Using the fruit fly, which in gene terms is actually quite similar to humans, Dr Palmer recently discovered that the ALK gene plays an important role in the growth of the embryo by controlling the formation of the gut. She is now investigating the role of the ALK gene in normal cells, firstly using the fruit fly as a model system. Dr Palmer will then analyse the same mechanisms in cells from more complicated animals such as humans. Once she has determined the role of ALK in healthy human cells, she will compare this with cancerous cells, in order to better understand the role of ALK in lymphomas.
Grant Holder: Professor Pasquale Verde
Institution: Institute for Genetics and Biophysics, Naples, Italy
Grant Award: £101,910 for 3 years
Project Title: The role of microRNAs in cancer
Cancer is caused by changes to either the structure or activity of certain genes that control how cells grow, divide and survive. These changes cause the cells to grow and divide in an uncontrolled manner and form a tumour. Scientists have recently discovered a new way that cells control the activity of many of their genes called microRNAs. Several hundred microRNAs have been identified and each one appears to be able to influence the activity of numerous genes in lab experiments. Some of these microRNAs appear to play a role in cancer, by increasing or decreasing the activity of key genes. However, the exact genes which the microRNAs act on is not yet clear. Dr Verde is determining which microRNAs control some of the most important genes involved in cell growth, division and death to determine what role the microRNAs play in causing cancer.
Grant Holder: Professor Alan Warren
Institution: University of Cambridge, England
Grant Award: £170,481 for 3 years
Project Title: Shwachman-Diamond syndrome (SDS) and acute myeloid leukaemia
Professor Warren is studying Shwachman-Diamond syndrome (SDS), an inherited childhood blood disease, which often develops into acute myeloid leukaemia. SDS is caused by inheriting a damaged version of the SBDS gene from one or both parents. The SBDS gene codes for a protein, also called SBDS. We do not understand exactly what the SBDS protein does inside our cells, but Professor Warren recently discovered that it plays a role in building structures called ribosomes. Ribosomes are involved in ‘uncoding’ the genes and helping create the corresponding proteins. Professor Warren noticed that other cancer genes are also involved in building ribosomes, so he has put forward the theory that mistakes in building ribosomes can somehow make a cell become cancerous. With his AICR grant Professor Warren is analysing exactly what role the SBDS protein plays in the way cells build their ribosomes. He wants to understand how a defective SBDS protein changes the building of ribosomes and how this causes Shwachman-Diamond syndrome which leads on to acute myeloid leukaemia.
Grant Holder: Dr Robert Feil
Institution: CNRS, Montpellier, France
Grant Award: £154,956 for 3 years
Project Title: Tagged proteins and their role in liver cancer
Cancer is caused by changes to either the structure or activity of certain genes that control how cells grow, divide and survive. One way that cells control the activity of genes is to add specific chemical groups or 'tags' on to the genes, and on the proteins which act as scaffolding for the genes. This ensures that genes are held in the correct shape and are made correctly. Depending on the type of tag, their addition can lead to an increase or decrease in gene activity. This often happens incorrectly in cancers and the resulting change in gene activity drives the cells to grow and divide in an uncontrolled manner. Dr Feil is studying two genes, called IGF2 and CDKN1C, which are known to have altered chemical tags in many types of cancer. He wants to identify the exact way in which they are modified and determine the underlying mechanisms. Dr Feil is also analysing the role of this type of chemical modification on genes in liver cancer.
Grant Holder: Dr Marco Malumbres
Institution: CNIO, Madrid, Spain
Grant Award: £166,601 for 3 years
Project Title: The role of microRNAs in leukaemia
Cancer is caused by changes to either the structure or activity of certain genes that control how cells grow, divide and survive. These changes cause the cells to grow and divide in an uncontrolled manner and form a tumour. Dr Malumbres is studying a new type of gene control, called microRNAs, and he discovered one microRNA that was either damaged or switched off in a variety of different leukaemias. His early findings suggest that the microRNA might be controlling the ABL gene which is involved in many different types of leukaemia where it is found glued or fused to another gene called BCR. Dr Malumbres is using his AICR grant to continue analysing this microRNA and how it controls the ABL gene, in healthy cells and leukaemia cells with the ABL-BCR gene fusion. He is also looking for ways to switch the microRNA gene back on to find out if that could stop the leukaemia cells from growing and dividing. And finally Dr Malumbres will investigate if there are other microRNA genes that could cause leukaemia and analyse how they are involved. The long-term aim of his study is to find ways to reverse the loss of the microRNA activity and determine if this could be an effective new way to treat these leukaemias.
Grant Holder: Dr Jean-Noel Freund
Institution: INSERM, Strasbourg, France
Grant Award: £214,434 for 3 years
Project Title: How is the Cdx2 gene involved in bowel cancer?
The cells lining our bowel are continuously growing, maturing then dying and being replaced throughout our lives. This is possible because bowel stem cells, a type of ‘starter cell’, are continuously multiplying to produce new cells. One theory is that bowel cancers start from bowel stem cells which begin to grow out of control. Dr Freund is therefore studying the mechanisms which regulate the maintenance of the bowel lining and how the bowel stem cells multiply to determine what goes wrong to cause bowel cancer and similar bowel-like cancers in other organs. Research has suggested that a gene called Cdx2 plays a key role in this process. Dr Freund has bred two new strains of mice. In one breed the Cdx2 gene can be switched off in bowel cells at defined times during the animal’s life. He will use these mice to study the role of the Cdx2 gene in controlling the bowel stem cells and find out how they sometimes give rise to bowel cancer cells. In the other breed the Cdx2 gene can be switched on in specific organs outside of the bowel, for example the stomach, pancreas and gall bladder. He will use this strain to investigate how these organs can also develop bowel-like cancers. Together these mice will provide valuable information about how bowel and bowel-like cancers start and develop.
Grant Holder: Dr Gary Clifford
Institution: IARC, Lyon, France
Grant Award: £161,188 for 3 years
Project Title: Different types of the HPV virus and their role in cervical cancer
Warts and similar conditions are caused by a type of virus called HPV, of which there are over 100 varieties. Two of them, called HPV16 and HPV18 are known to infect the cells of the cervix. In most women, this infection clears up rapidly, but in a very small number of women it becomes a persistent infection which then often leads to cervical cancer. Vaccines are now available to protect against HPV16 and HPV18 infections and are currently being used in a national vaccination program. However, there are several different types of HPV16 and HPV18 found throughout the world and we cannot be sure that the types that cause cancer in Europe and the USA are responsible for causing cancer in Asia, Africa and South America. Therefore Dr Clifford is analysing over 2,000 cervical cancer samples from a number of countries in Asia, Africa, South America and Europe to determine whether other types of HPV 16 and 18 may be involved.
Grant Holder: Dr Mark Hulett
Institution: Australia National University, Canberra, Australia
Grant Award: £126,701 for 3 years
Project Title: Is blocking the internal framework which supports cells a potential way to treat cancer?
Our tissues and organs are made up of millions of cells, held together by a material called the Extracellular Matrix or ECM for short. The ECM acts as a kind of cement between the cells and keeps them in a fixed position. One of the main components of the ECM is a long molecule called heparan sulphate. When cancer cells start to move and spread to other tissues in the body, they firstly have to push their way between the surrounding healthy cells, which requires them to break down the ECM. One of the ways they do this is by using a protein called heparanase, which acts like a pair of scissors and chops up the heparan sulphate. Blocking heparanase has been shown to stop the spread of cancer cells. Before we can develop new cancer drugs to block heparanase, we need to know a lot more about how it works. Dr Hullett has bred a mouse that can be made to stop producing heparanase in different types of cells e.g. blood cells, cancer cells, etc. He is now using this mouse to investigate the way that heparanse is made and used by tumour cells to help them spread.