Stéphanie Cornelis and Mubeen Khan
Retina UK is currently providing funding to Prof Frans Cremers at Radboud University in The Netherlands for investigation of the significant number of Stargardt disease (STGD1) cases where there is no obvious error in the most common disease-associated gene, ABCA4.
The project aims to develop a cost effective method of examining the entire ABCA4 gene to look for variations that might cause disease. In particular, the researchers will investigate variants hidden in the sections of the gene that do not actually code the building block ‘ingredients’ of the ABCA4 protein, but nonetheless can have a significant impact on protein construction.
Our funding has enabled Prof Cremers to employ two final year PhD students, Stéphanie Cornelis and Mubeen Khan, to work on the project. Both have already made significant contributions and have been inspired to continue their careers in retinal disease research when their PhDs are finished. Stéphanie and Mubeen talked to us about how they came to study this field and about life in the lab.
Stéphanie’s undergraduate and Masters degrees spanned neurology and genetics. She came to Prof Cremers’ lab as a research assistant and decided to stay to undertake a PhD. “He is very knowledgeable, motivated and enthusiastic, which is contagious. He is very good at seeing the potential in people and helping that potential flourish; it’s a very nice group to work in.”
This supportive environment was of particular help to Mubeen, who came to work on the project from her home in Islamabad, Pakistan. “I am really close to my family, so coming here and living independently was a big step” she told us. “Cycling into work every day was particularly strange to start with! But all of my colleagues have helped me to get settled.”
Motivated to make a difference
Both students are motivated by the impact inherited retinal disease makes on people’s lives. “During my Masters studies I had the chance to meet many people affected by different genetic disorders” said Mubeen.
“I realised how difficult it can be to live with any inherited condition, but the loss of vision is an especially big emotional and social trauma. That’s why I decided to further my studies in this field.”
Stéphanie agrees: “I became more aware of how special and wonderful it is to be able to see things and how disrupting and challenging it must be to have to let go of that. Being able to clarify what goes wrong in retinal disease is a big motivation, both because it gives patients an idea about what’s going on in their eyes and what might happen in the future, and also because it might eventually help develop therapies.”
Mubeen and Stéphanie each focus on different areas of the project. Stéphanie uses computer software to help her narrow down and combine vast amounts of genetic information, part of a discipline known as bioinformatics: “When the usual methods have failed to identify a mutation that explains someone’s sight loss, I look at all the variants in the DNA, which number well over 100,000. Most of these variants are benign and normal and it’s quite a challenge to find those one or two that cause blindness. Computer algorithms can help me filter the data.”
Mubeen is mainly involved in laboratory experiments to investigate the effects of newly discovered variants. “I’m looking for changes that may not directly affect protein structure but instead have an impact on the protein building process. I test the variants to clarify their role in disease progression.”
Without patients we can do nothing
Neither Stéphanie nor Mubeen could make progress without the contribution of people living with Stargardt disease. “It’s the most important pre-requisite for any study”
Mubeen tells us. “Without the contribution of patients we can do nothing. By studying their genetics we can really understand the underlying mechanisms of disease, which will ultimately benefit so many people because it allows us to look for treatment options.”
With your support, we can continue to support young scientists like Mubeen and Stéphanie who are solving the puzzles of inherited sight loss and working towards treatments. For more information about Prof Cremers’ project and other studies funded by Retina UK, visit https://retinauk.org.uk/research/research-we-fund/.