21ENGBIO Engineering Human Artificial Chromosomes (HACs) to Encode Genome Complexity

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A hallmark of many cancers is the presence of mutations in a person's genome, for example, where some of the 23 pairs of chromosomes have either lost or gained genetic material. Prostate cancer is the most commonly diagnosed cancer in the UK and Europe, and responsible for close to 110,000 male deaths annually (IARC, 2020). Up to 20% of prostate cancer cases present hallmarks of genomic instability due to mutations in the right arm of chromosome 8, which is associated with poor survival. We believe that extra genes may be driving prostate cancer, however, there are currently no models to define these relationships and their consequences in human cells culture. Synthetic Genomics is a bio-engineering field that uses genetic engineering and novel approaches to tackle the limitations of current methods in creating artificial DNA up to whole genome size. Synthetic Genomics enables the generation and editing of entire Human Artificial Chromosomes. By synthesising a similar length of a part of a human chromosome, but vary the order and number of the genes within the synthesized unit, the effect of gene number, location and translation can be studied. Success in this project would lead to a step-change for cell biology and the making and use of models to study human disease. This would include new models for cancer research (the exemplar used for this application).