My project aims to understand recently-identified links between image-based brain biomarkers and genetics. A recent landmark study conducted by an interdisciplinary group at the University of Oxford used the world’s largest human neuroimaging dataset, the UK Biobank, to identify associations between different MRI measurements of brain structure and specific genes.
Some of these genes are responsible for iron transport and accumulation in the brain, and are associated with neurodegenerative disorders such as Parkinson’s or Alzheimer’s disease. Other genes identified in this study appear to be linked to the structure of the environment surrounding the cells and particularly affect the brain’s white matter. However, it is difficult to understand the meaning of these links because neuroimaging markers are generally an indirect measure of biology.
We will investigate the same imaging biomarkers in mice where the equivalent genes will have been modified. The scanning protocols for rodents will include a range of MRI brain imaging protocols that are maximally equivalent to those used in the Biobank study. If we can identify equivalent MRI markers to those found in humans, our rodent images can then be compared to histological sections at microscopic resolution. A longer-term goal of this research is to perform scanning at different time points in the development of mice throughout their life, providing a direct correspondence with the Biobank study.
Ultimately, my project hopes to contribute to our insight into the genetic basis of brain structure across different species.
Protocol for tissue processing and paraffin embedding of mouse brains following ex vivo MRI.
Smart A. et al, (2023), STAR Protoc, 4
7,8-dihydroxyflavone enhances long-term spatial memory and alters brain volume in wildtype mice.
Rawlings-Mortimer F. et al, (2023), Front Syst Neurosci, 17