
ICR
ISNI: 0000000114990189 , 0000000112714623
Wikidata: Q6039999
RRID: RRID:SCR_003912 , RRID:nlx_158259
ISNI: 0000000114990189 , 0000000112714623
Wikidata: Q6039999
RRID: RRID:SCR_003912 , RRID:nlx_158259
129 Projects, page 1 of 26
assignment_turned_in Project2011 - 2015Partners:ICR, ICRICR,ICRFunder: UK Research and Innovation Project Code: G1100386Funder Contribution: 213,100 GBPNeuroblastoma (NB) is the second most common childhood cancer. It develops from the sympathetic nervous system and the majority of children with high-risk disease die from cancer relapse despite intensive treatment. Changes in two cancer-causing genes, MYCN and ALK, are closely associated with poor outcome. The role of MYCN in causing high-risk NB is well recognised, but ALK was only recently identified. It is unknown whether ALK can cause NB alone, or requires an interaction with MYCN. Clinical evidence suggests that patients with concurrent abnormalities in both ALK and MYCN genes have uniquely aggressive disease and very poor survival. Our laboratory has developed the first genetically engineered model of NB in which both MYCN and ALK are abnormal. As in patients, tumours are aggressive and survival is poor. I hypothesise that ALK cooperates with MYCN to cause NB and will use our model to establish how MYCN and ALK cooperate and to evaluate whether drugs that attack ALK, Mycn or both proteins are needed to stop tumour growth. If my work succeeds, we will identify new, molecularly-targeted drugs that could be utilised in clinical trials for patients with relapsing NB. Currently these patients have no options for treatment.
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For further information contact us at helpdesk@openaire.eumore_vert All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=ukri________::86354440de5a0f1864d77721ebfcfbf4&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euassignment_turned_in Project2008 - 2011Partners:ICR, ICRICR,ICRFunder: UK Research and Innovation Project Code: G0800021Funder Contribution: 391,328 GBPViewed through a microscope, cells undergo a spectacular transformation as they enter mitosis, the phase of their existence just before they divide. The formation of the mitotic spindle, where the cell?s network of microtubule fibres is completely rearranged to span from either end to the chromosomes at the centre, is particularly striking. This spindle is a molecular machine that ensures the cell?s chromosomes are accurately distributed between its two daughter cells. Errors in the workings of the spindle are a known driving force of cancer and are also responsible for a congenital brain disease. Several control mechanisms ensure the mitotic spindle is normally assembled correctly. At an early stage in assembly, two proteins called TACC3 and ChTOG promote microtubule stability and hence promote assembly. These proteins are more effective when TACC3 is modified by a phosphate group: one phosphorous atom and three oxygen atoms that is commonly used by cells to alter the activity of their proteins. In the case of TACC3, the protein that adds the phosphate is called Aurora-A. Spindle assembly is thus controlled by the activity of Aurora-A, which is itself controlled by many other proteins under the influence of events within and outside the cell. We propose to investigate how the phosphate group influences the effectiveness of the TACC3/ChTOG partnership at the level of atoms. How this works is currently a mystery as the phosphate is only four atoms big, and yet it changes the activity of TACC3/ChTOG which total tens of thousands of atoms. We will use electron microscopy, a technique that allows us to see directly the shapes of proteins, to study the changes in TACC3 upon phosphorylation, and the effect on ChTOG. We will also use X-ray crystallography to determine the location of every atom within the proteins and to map the atoms by which TACC3 and ChTOG cooperate. This information will allow us to make a hypothesis for the details of how the TACC3/ChTOG partnership works and how phosphorylation enhances their effectiveness. We will use our protein structure models to design subtle modifications to TACC3 and ChTOG to test this hypothesis in human cells grown in culture. An overabundance of TACC3, ChTOG or Aurora-A have been linked with cancer, and TACC3 and Aurora-A are also important in brain development. These studies will provide the impetus for future investigations to understand the role of these proteins in human disease.
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For further information contact us at helpdesk@openaire.euassignment_turned_in Project1997 - 2009Partners:ICR, ICRICR,ICRFunder: UK Research and Innovation Project Code: G9600656Funder Contribution: 2,079,380 GBPThe patient advocate group Radiotherapy Action Group Exposure (R.A.G.E.) has become a strong supporter of the START initiative over the years, with 2 members represented on the Trial Management Group. Issues relating to radiotherapy fractionation have emerged repeatedly in the media over the last 20 years. The understanding of scientific issues by the majority of lay people and a minority of professionals has been poor. The trial has achieved a high public profile across the UK including a discussion on Panorama. A highly productive debate has changed the climate, with the importance of evidence based medicine acknowledged by all parties.
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For further information contact us at helpdesk@openaire.eumore_vert All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=ukri________::39ef0c935aeb944faf27db2d20019c93&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euassignment_turned_in Project2022 - 2026Partners:ICR, ICRICR,ICRFunder: UK Research and Innovation Project Code: 2748396New drugs are starting to change the way cancer is treated. With our partner Artios, we have recently identified a new class of cancer drugs, known as Pol0 inhibitors, which work by targeting the DNA repair processes in cancer cells. These drugs kill tumour cells with BRCA1 or BRCA2 mutations but also kill tumour cells that have developed resistance to a commonly-used targeted therapy, PARP inhibitors. In order to ensure that this promising approach to cancer treatment is used in the most appropriate patients, we need to better understand at the molecular level how Pol0 inhibitors work and how tumour cells might re-wire or evolve in response to Pol0 inhibitor treatment. This PhD is aimed at answering these questions, and will give the candidate high-level training in functional genomics, drug discovery, cancer biology, genetic manipulation, high-content microscopy, image and data analysis, DNA repair biology, cancer drug resistance and synthetic lethality, forming the basis for a later career as a cancer researcher.
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For further information contact us at helpdesk@openaire.euassignment_turned_in Project2005 - 2008Partners:ICR, ICRICR,ICRFunder: UK Research and Innovation Project Code: G0401179Funder Contribution: 231,123 GBPThe adrenal is an essential organ in vertebrates required for maintenance of homeostasis. Defects in adrenal differentiation can be lethal if left untreated. Relatively few transcription factors have been identified to be important in adrenal development and function. The transcriptional coactivator CITED2 has been implicated in the development of the mammalian embryo in various tissues. Mice deficient for Cited2 show absence of adrenal development. The aim of this project is to determine the role of this factor in adrenal differentiation and to establish the molecular and cellular pathways that it regulates within this tissue. These studies will provide insight into the process of mammalian adrenal development and will allow us to further understand the basis for deficiencies in adrenal development in man. Members of the CITED family have been implicated in carcinogenesis through their role in the regulation of cell proliferation and control of hypoxia inducible pathways such as angiogenesis. Therefore we propose to investigate if CITED2 has a role in adrenal cortical tumour formation in humans. Tumours of the adrenal cortex are relatively common and mostly benign. However, a proportion gives rise to malignant adrenal carcinomas that have extremely poor prognosis. Given that developmental pathways are often implicated in carcinogenesis, we will analyse the pathways that we have identified to be activated by CITED2 in embryonic adrenal differentiation in the adrenal tumours. The aim of these studies is to provide diagnostic markers that may help the treatment of this disease.
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