Investigating the ageing brain

We talk to Dr Tara Spires-Jones, Chancellor’s Fellow and interim Director of the Centre for Cognitive and Neural Systems. Her research group studies brain changes in ageing and neurodegenerative diseases including Alzheimer's.

Paved roads

Tara grew up in “the middle of nowhere” in Texas, 10 miles outside a small town called Leander. She has fond memories of her rural upbringing, saying: “The area where I spent my early years may not have had paved roads but it did have an abundance of nature, snakes and insects – and I loved it.”

Tara left Leander to study chemistry at the University of Texas, and in 1999 she graduated in Biochemistry, having switched degrees to satisfy her enthusiasm to study the brain.

Oxford calls

A pivotal moment in Tara’s career was when she emailed pioneering neurobiologist Professor Sir Colin Blakemore enquiring whether she could complete her PhD with him.

Following a successful interview, Tara moved to Oxford where she investigated Huntington’s disease, becoming fascinated by how the brain is affected by disease.

Tara’s PhD focused on the connections between nerve cells, known as synapses. These connections become stronger as we learn new things and form memories. When synapses are disrupted (as in diseases such as Alzheimer’s) this can contribute to a decline in memory and thinking skills.

Tara explains: “When looking for the next step after my PhD, I thought dementia was an area where I could really make a difference. I really aimed to use my knowledge and skills to try and understand how these connections go wrong in Alzheimer’s and whether there are ways to protect them.”

From Oxford to Harvard

Tara returned to the USA after her PhD and spent almost a decade investigating synapse degeneration with neurologist Professor Brad Hyman at Harvard University. Promotion and funding allowed her to run her own lab for the first time and work with a huge multi-disciplinary team carrying out cutting-edge research across several neurodegenerative diseases.

Chancellor’s Fellow

By 2013, Tara and her family were ready to move back to the UK and she successfully applied to the Chancellor’s Fellowship programme at the University of Edinburgh.

While Tara continues to collaborate with colleagues around the globe, she enthuses about the opportunities at Edinburgh:

“I am part of an incredible, unique and vibrant community where collaboration across the wider University is actively encouraged and facilitated. The access to cohorts of human subjects is excellent as are the patient groups and clinicians I work with. Edinburgh is a fine example of multi-disciplines working towards a common goal.”

Imaging synapses

A large part of Tara’s work is focused on understanding why synapses are vulnerable in Alzheimer’s disease and ageing. Loss of synapses is a strong predictor of dementia synapses, and understanding the reason they degenerate may lead to effective treatments.

While at Harvard, Tara pioneered the use of the high-resolution imaging technique called array tomography for examining human brain tissue. When she moved to Edinburgh, she brought this unique technology with her, and has worked closely with neuropathologist Professor Colin Smith to establish a bank of donated human brain tissue prepared for this specialist imaging, making Edinburgh one of the few places in the world to hold such a bank.

Using these precious donated brain samples, researchers can explore in unprecedented detail the changes that occur in synapses. To do this, tiny pieces of brain tissue are embedded in a hard plastic resin and cut with a diamond knife into a series of ultrathin sections.

The molecules in these sections are labelled with glowing tags and a microscope is used to take images and reconstruct a three-dimensional picture of degenerated synapses.

“This post-mortem brain imaging gives researchers a snapshot of what was wrong in synapses in the disease,” says Tara. “But to figure out whether these discoveries will be useful to treat people, we need living cells to test treatments”

Tara uses both mouse models of disease and human brain cells made by reprogramming donated skin cells. In these models, scientists take discoveries from the human brain and test whether they can prevent or reverse synapse loss. Results that look promising in models are then given to colleagues running human clinical trials to test in patients, including those in the University’s Centre for Dementia Prevention.

Outwith the lab

Tara has become involved in various activities beyond the lab. She has been recruited to several boards, including the Scottish Science Advisory Council, the Federation of European Neuroscience Societies, the Kavli Network of Excellence, and is Chair of the Alzheimer’s Research UK Grant Review Board.

“I am keen to engage with the public and policy makers,” she says. “It’s vital to ensure that people understand the value of science and its necessity both for understanding more of how the brain works and for treating diseases. I also work with groups of scientists and funders to push research forward by making experiments in dementia research more rigorous and collaborative.

“Having been inspired by my own mentors, I’m dedicated to improving career development opportunities for young scientists, and like to promote opportunities for women in science. I also love engaging members of the public in my research – through that I can help promote the role of science in society.”