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Studying heart muscle under the microscope

Dr Danielle Paul

Following a planned career break, Dr Danielle Paul is back studying heart muscle under the microscope. She talks to Sarah Kidner about her work and her ambitious plans for the future.

For as long as she can remember, Dr Danielle Paul has been fascinated by science. “My mother was a research physicist,” she says. “The thought of becoming a scientist seemed natural, but if you’d asked me back then what I wanted to be, I would probably have said a doctor.”

She discovered a passion for physics, completed a physics undergraduate degree and then began a BHF-funded PhD looking at cardiac tissue under the microscope. “It seemed an interesting application of physics and biological techniques,” she says.

Heart muscle in 3D

Using specialist microscopes that use electrons instead of light, Dr Paul examines proteins within heart muscle. “We’re looking at the molecular structure through a microscope and building a picture of how, at that level, the heart muscle is functioning in a relaxed and an active state,” she says. Dr Paul uses these images to create 3D ‘molecular movies’ of how the heart functions normally and when it is diseased.

Dr Danielle Paul using the microscope“There are some amazing operations where a part of the heart tissue is removed to remould the heart. In cardiomyopathy, one of the treatments has been to shave part of the heart away, because it improves the function of the heart. That is one possible source of tissue for us to examine.”

Dr Paul is specifically interested in proteins that regulate muscle contraction and attach to structures in the heart tissue called actin filaments. “The images we obtain are used to make 3D maps of the proteins we are interested in,” she says.

“We can evaluate and interpret those maps by using other available information, a bit like fitting pieces into a three-dimensional jigsaw puzzle. We use known structures of actin to help identify the proteins that we are interested in.

“Our 3D maps are deposited into online databases which are freely accessible so that any researcher can download one of our maps and see if it agrees with their research.”

A revolutionary approach

Imaging techniques are constantly advancing, something Dr Paul is especially conscious of, having taken a career break. In April 2012, she decided to take time out to spend with her newborn daughter, Hadley (now three), and her son, Harrison, who was aged two at the time.

“It was a big decision, but it was important to me. Although it was a long break, I was staying in touch with my colleagues, so while it was time out, it was a step to the side,” she says.

BHF Career Re-entry Research Fellowship funds three years of Dr Paul’s workIn the two-and-a-half years she’s been away, there’s been a revolution in electron microscopy. “Within the field, they had what was called the cryo-EM revolution. While I was out, I missed the revolution, but I am profiting from the advances,” says Dr Paul.

“There is a whole new breed of detectors for the microscopes and advances in the processing software. This has all come about in the past two to three years and to be able to learn from that is great.”

The University of Bristol, where Dr Paul now works, is planning to apply for funding for an electron mini-microscope that uses this technology. Dr Paul’s post is funded by a BHF Career Re-entry Research Fellowship.

The grant of £207,979 over three years pays for her salary and equipment. “As I’d had two years out of science, not in an academic position, I was eligible for the re-entry fellowship,” she says.

“The BHF has supported me throughout my career. My PhD was BHF-funded, and during my post-doctoral years I received project grants. It’s great to continue that relationship.”

Career aspirations

Dr Danielle PaulDr Paul believes building a structural picture of heart muscle at a molecular scale could help inform new drug design and would love to set up a research group to explore this further.

“The beauty of looking at things through an electron microscope is that you can actually see what’s happening and where drugs bind,” she says.

“I would love to have a small group of PhD students and post-docs to explore the effects of drugs on muscle tissue and see what cardiovascular drugs are doing at the molecular level.”

She’s also hoping to team up with a colleague who is being funded by the BHF through an Intermediate Research Fellowship. Together they will use her established techniques to look at the detailed structure of zebrafish hearts, a collaboration that’s come about because of their shared relationship with the BHF.

Dr Paul has a message for all our supporters: “We couldn’t do it without them. Everything we do is reliant on the BHF.”

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