Prof. Jane Farrar
Professor Jane Farrar is Head of the School of Genetics and Microbiology at Trinity College Dublin. This project is part of the Target 5000 program and is examining the DNA of people affected by inherited retinal diseases on the Island of Ireland to try and find a genetic cause for their conditions.
Project: ‘Elucidation of the genetic pathogenesis of IRDs in a cohort of Irish patients’
Start date: 2022
Amount: €402,330
Fighting Blindness and Prof Farrar have a long history of collaboration, in fact Fighting Blindness funded Prof Farrar’s PhD. We have also previously funded a number of Prof Farrar’s projects including another Target 5000 project.
Professor Jane Farrar is the Head of School Genetics & Microbiology, at Trinity Inst. of Neurosciences (TCIN), Trinity College Dublin, Ireland.
Two of the key aims of the Target 5000 program is to ‘provide a genetic and clinical diagnosis to individuals with an IRD in Ireland’ and ‘to discover new genes responsible for IRDs’. This project addresses these two aims and therefore is a very significant investment for Fighting Blindness.
Dr Laura Finnegan is the post-doctoral researcher working on this important project. We asked Dr Finnegan to explain the project.
- What are the overall aims of the project you are working on, including how it could have an impact on those affected by sight loss?
- Why did you get into research and what do you most enjoy about it?
- Within the next five years, where do you expect great advances to be made in vision research?
- What are your other interests?
- Short bio
1.What are the overall aims of the project you are working on, including how it could have an impact on those affected by sight loss?
Our current Fighting Blindness project focuses on two types of techniques that examine the DNA of people effected by sight loss. These techniques are called whole exome sequencing*, which looks at DNAin the parts of the genome that encode proteins, and whole genome sequencing*, which looks at DNA in the entire genome.
In a previous project, the Farrar lab analysed whole exomes of 150 people for potentially disease-causing variants (changes in the DNA sequence) in over 250 genes. The likely cause of disease was identified in approximately half of the people included in this group.
- The current project builds on this, interrogating the whole exome of a further 150 people. It is hoped that like in previous projects the majority of these 150 people will have a disease-causing variant detected.
- The project will also re-examine the people for whom no variant was detected in the previous project, this time they will be analysed to look for new genes that have very recently been linked to inherited retinal degeneration.
Once a variant is found, its potential to cause disease must be evaluated. In the Farrar Lab, we use a variety of computational tools to explore the potential disruption that variant might cause in vision. We examine the literature and databases containing information on the DNA of a large number of people (population databases) to see if anyone else has reported this variant and conducted any studies that look at the function of the variant and see if it involved in disease.
Find out more about the story to date between Fighting Blindness and Prof. Jane Farrar’s lab at Trinity College Dublin at the video below:
Additionally, where family members are available, we sequence these individuals for the same variant to see if the variant is only present in those affected by the disease. Sometimes it is unclear whether a variant is disease-causing or not but samples from family members can help us to figure this out. It is extremely useful to have sequence from family members, including those not affected by retinal degeneration, and we are so thankful to everyone who participates in our work.
In all, this project will provide more people living with inherited retinal degeneration with information about the genetic cause of their disease.
- This information is not only valuable for their own understanding of their disease, but is essential if they wish to avail of possible treatment options as they arise in the future.
- In addition to the direct impact on those involved in the T5000 study, projects such as this provide the scientific community with further knowledge about the cause and progression of disease, which is vital for the development of therapies.
2.Why did you get into research and what do you most enjoy about it?
I joined the Farrar Lab in 2017 having spent a summer working in the Stamer Lab in Duke University during my undergrad. While experiments don’t always work the way you expect, the excitement of finding out a new piece of information that could potentially help in the fight against blindness makes it worth it! Any given day could involve anything from preparing samples for sequencing to meeting with a clinician to report any findings. We are always busy with lots of interesting work to do!
I love problem solving and working with my hands, so lab work was a natural fit. – Dr Laura Finnegan
3.Within the next five years, where do you expect great advances to be made in vision research?
I expect leaps to be made in our understanding of inherited retinal degeneration as more whole genomes are sequenced and interrogated. We will undoubtedly discover variants deep in the introns** of known disease-causing genes and perhaps even in some new genes previously not known to be associated with inherited retinal degenerations.
Some conditions are quite variable in their presentation, where some family members might have more severe vision loss than others despite having the same disease-causing variant. Sequencing whole genomes could potentially identify modifier genes that are affecting how the original disease-causing variant presents itself.
An example of this has been seen in golden retriever muscular dystrophy, where some puppies escaped the disease due to the presence of a modifier variant (Vieira et al., 2015). Understanding modifiers would not only help us to understand how a disease might progress in a given individual but might also initiate the development of new therapies.
Find out more about the future of genetic research in Prof. Jane Farra’s lab (Trinity College Dublin) funded by Fighting Blindness, at the video below:
4.What are your other interests?
When I am not in the lab, I can be found drawing or painting, walking my golden retrievers or helping my dad inspect his beehives. I have worked as a scientific illustrator on a variety of projects, which have been a pleasure: uniting my two passions.
You can click here or view below a short stop-motion animation I made about my work!
Interested in how gene therapy can help fight inherited retinal regeneration? Here’s a little stop motion animation about what we do in the Farrar lab @tcdgenmicro @tcddublin 🧬 Thanks to @fight_blindness for the prompt ✨🧡 @PhD_With_Laura @askits4women #ShareYourResearchSeries pic.twitter.com/dq2afd6eu7
— Laura Finnegan (@laurakfinnegan) February 26, 2021
5.Short bio
I am the post-doctoral researcher working on the TCD branch of the Target 5000 project. During my PhD, I explored three potential gene therapies for optic neuropathies. While I am still involved in the gene therapy work in the Farrar lab, at the end of 2022 I joined the Target 5000 project to help identify disease-causing variants in our Target 5000 participants.
I am particularly interested in gene-independent therapies, therapies that target disease mechanisms common to many diseases. In principle, such therapies may be applicable to a wide cohort of patients. My PhD in the Farrar Lab explored some such therapies. While many retinal degenerations are caused by variants in a single gene, others such as age-related macular degeneration involve a variety of factors from genetics to smoking to diet.
Therapies that target the underlying pathway disrupted in these conditions are very exciting and could potentially treat millions of people around the world. Indeed, the Farrar Lab is working on one such therapy, featured on RTE.
Follow Dr Laura Finnegan on her Twitter account @laurakfinnegan to stay in touch with the most recent updates on her work!
My days are very varied so I am never bored! – Dr Laura Finnegan
*To find more information on what exomes and whole exome sequencing are, please click here
**To find more information on what introns are, please click here