A UK-wide centre will help scientists delete every gene in human cells grown in a dish, one by one, to see which ones drive disease. This matters because CRISPR screens—which use a bacterial defence system to cut DNA at precise points—are already a standard tool for finding cancer drug targets. But for most other diseases, the technique has been limited by a lack of good cell-based models that mimic real human biology. The centre will solve that by pairing improved “disease-in-a-dish” models with arrayed CRISPR screens, where each gene is systematically removed and the effect on disease biology measured. If the centre succeeds, it will generate a public database of which genes matter for conditions such as diabetes, neurodegeneration, and autoimmune disorders. That knowledge will help biotechnology and pharmaceutical companies identify new drug targets and develop treatments. The centre will also share its techniques and protocols openly, so any lab can run these screens themselves—democratising access to a tool that has so far been concentrated in cancer research.
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"The discovery in bacteria and archaea of a mechanism that can read stretches of DNA and introduce breaks at specific points as a form of defence against infection led to the development of what we now refer to as CRISPR screens. The mechanism that underpins CRISPR screens enables the possibility of deleting genes to interrogate their impact on the behaviour of cells. This has been widely adopted as one of the techniques used to identify potential new therapeutic targets for the treatment of cancer. However, this approach is not as widely used for other human diseases because of the limited availability of suitable biological models. However, models of human disease that can be studied in a dish as opposed to an animal are improving such that it should be possible to genetically interrogate these models using a form of CRISPR screen, known as an arrayed screen. These screens involve using cellular models of disease and genome-wide CRISPR libraries to ask the question – what is the effect on disease biology if each gene in the genome is systematically deleted? The data generated by this centre will be used to refine models of human disease and generate know-how based around the use of arrayed genetic screens to better understand disease development and response to treatment. We will instigate a UK wide call for applications from academics and the commercial sector interested in using arrayed screening approaches to address a specific disease related question. Decisions regarding which models are suitable for screening will be made by a joint steering committee with expert knowledge of complex disease models and arrayed screening techniques. We will assist with the screening process for successful applicants, including library and bioinformatics support. We aim to democratise the use of arrayed CRISPR screens by sharing data and making techniques and approaches available to others so that they can use these approaches within their own laboratories. Building this wealth of knowledge will improve our collective understanding of human disease and support biotechnology and pharmaceutical companies in translating these biological findings into new treatments."
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