Researchers at the Francis Crick Institute, led by group leader James Turner, will for the first time use gene editing techniques in opossum embryos. The work is part of a £2m Wellcome Investigator Award to study X-chromosome inactivation, providing insight into embryo development, regenerative medicine and infertility.
Female and male mammals are genetically similar, with the exception of their sex chromosomes: females have two X chromosomes (XX) while males have one X and one Y (XY). In females, one of the X chromosomes needs to be ‘turned off’ in every single cell in their body.
Problems in this process can lead to developmental disorders and cancer, but the details of how it works are poorly understood.
James’s team will study opossums, a marsupial whose evolutionary tree diverged from placental mammals more than one hundred million years ago. Both groups independently evolved X-chromosome inactivation, so researchers will compare mechanisms to better understand the process. One approach they will use is CRISPR-Cas9 genome editing, which they will apply for the first time to opossum embryos in order to identify critical players in the X-inactivation pathway.
“When we see traits evolving independently, any similarities in them are likely to be important features. A well-known example is how bats and dolphins both use echolocation to locate objects,” says James.
“By studying this convergent evolution, we can uncover successful strategies for dealing with a problem the animals face – in this case how best to silence one X chromosome in females. In turn this will help us understand how this process might go wrong, and potentially identify ways to fix it.”
Marsupials are also excellent models for studying cancer, immunity and spinal cord regeneration. The scientists hope their work will lead to insights that help other research teams studying these areas of health.
The Crick is home to one of northern Europe’s only colonies of opossums used in scientific research.