Unravelling the links between genetic mutations and brain structure across species

I am a DPhil student from Romania, currently undertaking my studies at University of Oxford’s Wellcome Centre for Integrative Neuroimaging. I was born in Brasov, a beautiful mountain city in the heart of Transylvania. With the help of an undergraduate bursary scheme, I came to the UK in 2014 to start a 4-year integrated master’s degree at University College London, focusing on Neuroscience and Medical Physics. I was the first person in my family to complete a university degree. 

Throughout my undergraduate studies, I developed an interest in both neuroscience and medical imaging and engineering, which I’ve been nurturing to this day. My first undergraduate research project, conducted during the summer after finishing my 2nd year and funded by UK’s Engineering and Physical Sciences Research Council, focused on improving the technologies used during brain tumour surgeries. Having taken a magnetic resonance imaging (MRI) module in my 3rd year, I was enthralled by the technique and decided to specialise in MRI neuroimaging, consequently completing a summer project on MRI imaging in epilepsy and a master’s project on MRI imaging of patients with brain tumours.

I came to the University of Oxford in 2018, with the aim of continuing to research brain structure and function using MRI. I joined the group of Prof Karla Miller in October 2019, after completing specialised courses and rotation projects which are part of my DPhil training. I am a proud member of the Physics group at the Wellcome Centre for Integrative Neuroimaging, a research facility which aims to take insights from basic neuroscience and use them to generate a meaningful impact on human health, by undertaking studies spanning from animal models through to human populations. Neuroimaging offers a powerful means of connecting these different scales, providing measurements that are sensitive to cellular phenomena and can be performed in living subjects and human populations. 

UK Biobank is a major research study within our centre – a research endeavour gathering questionnaires, physical and cognitive measures and biological samples from 500,000 participants and imaging data from 100,000 participants, with their health outcomes being tracked over decades. Our centre was responsible for putting together the MRI acquisition and analysis protocols for the neuroimaging component of this study – currently the world’s largest human neuroimaging dataset. Current studies are focusing on associations between this neuroimaging data and either lifestyle factors or genetic information collected from the volunteers. 

A landmark study conducted at our centre and published in the journal Nature (https://doi.org/10.1038/s41586-018-0571-7) showed associations between various MRI measurements of brain structure and mutations in 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 neurons and particularly affect the brain’s white matter. However, it is difficult to understand the meaning of these links because neuroimaging measurements are generally an indirect measure of biology.

My DPhil project, co-supervised by Prof Miller and Dr Aurea Martins-Bach, investigates the same imaging measurements in mice where equivalent genes can be modified. The scanning protocols for rodents 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, the rodent MRI images can be compared to microscopy images – thus providing an interpretation of the biological changes that affect the MRI signal. 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 aims to contribute to insights into the genetic basis of brain structure across different species.

Outside of my studies, I am particularly passionate about discussing and addressing issues faced by women working in science and engineering. To this day, women are underrepresented in numerous scientific areas, particularly in leading positions in both industry and academia. I am currently trying to do my part to help address these issues by coordinating a group of women in physics and engineering within our centre. We organise meetings where we discuss important issues for women in research and academia, such as interview practices, career options or caring responsibilities. We sometimes have invited speakers: 12 prominent women researchers from across the world joined us for in-person and virtual meetings during 2020. Within this group, we aim to learn from each other and openly discuss the issues we face – and hopefully inspire more and more brilliant women from across the world to choose a career in science.

Cristiana Tisca