PhD student Elena Piotter

Meet a Researcher: Elena Piotter

Nurturing a new generation of scientists is a vital investment in the future of retinal disease research, so we are delighted to be funding, in collaboration with the Macular Society, a new PhD studentship at Oxford University, supervised by Professor Robert MacLaren.

Student Elena Piotter began work on the project in October 2020 and will be investigating a potential Stargardt disease treatment, which could also be helpful for other inherited retinal conditions. Here, Elena tells us a little about her background, her aims for the project and hopes for the future.

“I completed my undergraduate studies at the University of California – Davis, where I started with a degree in International Relations but quickly realised I missed science so much that I added on another degree in Global Disease Biology. My biochemistry course and time spent working in a protein engineering lab really piqued my interest in laboratory work and understanding things on a molecular level; I loved learning how you could work with what nature had provided to try and solve problems.

“I decided to pursue a Master’s degree in molecular biology at the University of Groningen in the Netherlands, which involved studying the biochemical “tools” that certain bacteria naturally produce to enable them to interfere with genetic code via a molecular pathway known as CRISPR. (Bacteria use this as a defence against viral attacks.) As part of my studies, I came over to Professor MacLaren’s lab to look at how this might be applied to gene therapy. This project was really exciting for me, as it exposed me to real-life outcomes and how they might help people.

“I initially knew very little about retinal conditions, sight loss or eyes in general – the most I had been exposed to was dissecting a cow eye in anatomy class! But within the first few weeks of the Master’s project in Professor MacLaren’s lab, I learned so much. I heard about the development of therapies that had progressed to clinical trials and about the diversity of people affected by inherited sight loss, which really added a new depth and purpose to the project. Professor MacLaren also let us watch some clinical trial surgeries at Oxford, which only added to that sense of resolve and responsibility, and drove me to work harder. It also became clear to me that I wanted to continue the work with a PhD.

My PhD project will investigate the use of CRISPR gene editing tools, similar to those I studied during my Master’s, to correct disease-causing faults in the genetic code. So far, gene therapy has allowed for the replacement of faulty DNA by using a harmless virus to carry healthy copies of the affected gene into retinal cells. However, a number of genes are too long to fit into these viruses, including the ABCA4 gene, which is associated with most cases of Stargardt disease. “

“As an alternative to replacing the whole gene, I will see if we can use CRISPR technology to target the specific section of ABCA4 genetic code that is faulty and correct the error. Specifically, we want to try editing the genetic molecule known as RNA, which is a copy of the genetic instructions (DNA) that is carried to the cell’s protein-building machinery to produce protein. RNA makes a nice target for editing as, unlike DNA, it only exists temporarily, so our interventions would not introduce permanent change. This would potentially increase safety. RNA also offers more flexibility in terms of what can be targeted.

“There’s still a lot to learn, but exploring these new techniques allows us to broaden the realm of what’s possible and enables more creativity in problem solving. This approach to treatment also has potential for a number of inherited retinal conditions, not just Stargardt disease.

“I am really enjoying the whole PhD experience – lab meetings, discussions, and of course seeing results in the lab. It’s exhilarating when you’re checking to see if an experiment worked and an amazing feeling when it has been successful. On the other hand, it’s really frustrating when it doesn’t work and you have to repeat it. The other people in the lab are amazing though and overall it’s a fun and engaging process.

“I would like to say a huge thank you to the Retina UK supporters who have helped to fund this project – I am truly grateful to be able to work on it every day. Your donations are so generous and will allow us to undertake really important research.

“I really hope my work has an impact in some way for people living with Stargardt disease and other conditions; I hope it provides some optimism in the short term and contributes to a sight restoring treatment in the long run. I would love to eventually meet some families affected by inherited sight loss – hopefully this will be possible after the pandemic has subsided. I’m also hoping to run for Retina UK in a fundraising event, so hopefully I might meet some of you then.”

Update – 2023

Some readers may remember Elena Piotter, who started her PhD in 2020; a project also co-funded by Retina UK and the Macular Society. She describes her experience working on a project at Oxford University investigating the efficacy and safety of potential gene editing approaches for the treatment of Stargardt disease.

“The project has been super exciting and not at all as I anticipated! I met and worked with some amazing people.

“It has had its ups-and-downs, but so far, we’ve shown that mutations in ABCA4 can be corrected by DNA and RNA editing. We have also found that it is very mutation dependent. In some cases, one or both editing systems work really well. In other instances, neither will work. We are currently trying a different kind of editing to circumvent this. The next step will be
looking at testing this new method in retinal organoids, which I’m very excited about!

“I always loved science and wanted to pursue a career in this area, but didn’t know exactly what or how. When I started IRD gene therapy research pre-PhD, I didn’t know anything about eyes or CRISPR, but quickly came to love it. The PhD has allowed me to pursue this for longer and in more detail!

“I am really looking forward to what the future holds. I’m not quite sure what I’ll be doing next but in the short term I have extended the project until the summer to finish gathering data!
I’m looking forward to seeing the final result and will update Retina UK after that.”