Researcher report: an interview with Dr. Niamh O'Sullivan

Image Credit: Vincent Hoban

Jade Norton meets UCD lecturer and researcher Dr. Niamh O’Sullivan, and delves deep into the heart of her research and her passion for understanding motor neuron diseases through the small medium of flies.

Dr. Niamh O’Sullivan is a lecturer and researcher in the Conway institute in UCD, whose research is centred in the ‘Fly Lab’. She graduated with a degree in genetics from Trinity College Dublin before pursuing a PhD in Neuroscience in UCD. During her PhD work she was invited into the animal house in UCD which houses all animals used for research in the university and where O’Sullivan first became acquainted with the flies that were to become central to her work.

Flies are not commonly considered as a typical model organism for disease research outside of scientific communities, as most often mice or monkeys will be thought of due to their similarities with humans or their shared mammalian heritage. However, despite physical differences flies have similarities to humans at a genetic level that can be used when discovering the root causes of diseases. Dr. O’Sullivan has often dealt with this initial doubtfulness and lets me know that; ”About 75% of all disease causing genes in humans are conserved in flies” - which means that by understanding how mutations in DNA affect flies, you can compare to humans to see the same or similar effect.

Animal models are essential to disease research as they allow for experiments to be done on  anatomy or biological systems that are similar to humans, providing beneficial knowledge that is collected and transferred to other animal models that are more similar to humans. Once the information is gathered, further development of drugs or treatments on humans can begin with a higher degree of certainty that they will be effective.

The focus of Dr. O’Sullivan’s research is on motor neuron diseases, such as Lou Gehrig’s disease or ALS, that cause degradation of the motor neuron cells which connect the brain to the limbs. There are two motor neuron cells each involved in the control of movement for every muscle in the body. There is one connected to the part of the brain that processes the decision and the other that travels from the base of the brain through the spinal cord and directly to the area it is needed. The length of these cells varies. Dr. O’Sullivan mentioned that in flies these cells will be microscopic in length but the equivalent in humans can be up to 1m in length. The large length of these cells makes it difficult and potentially dangerous to work with in humans, whereas in flies their tiny size makes it much more accessible. Incorrect functioning along either of these cells means that “connections between the brain and the muscles throughout the body [are] breaking down, that is, the signalling doesn’t get properly from the brain to the muscle” which can lead to varying levels of paralysis and/or movement defects in patients. 

Dr. O’Sullivan stresses that using animals in research is not seen as a fickle matter, but that it is heavily regulated to ensure that only the number of animals needed for an experiment are used to prevent excess waste. Every researcher, including Dr. O’Sullivan, has a licence given to them by the Health Products Regulatory Agency (HPRA) specifying that they have the legal right and intent to use animals in their research. With this tight regulation she emphasises that “you have prevented a whole lot of waste- not only animal waste but also time”.

On her reason for choosing flies as a model organism she said that “I wasn’t happy working with rodents – I wanted to look at other options”. Helpful to her choice was the fact that there is a high similarity between fly and human neurological systems that made the use of this model organism more applicable. She maintains that it is quicker, cheaper and more humane to use flies over other organisms as flies take only 13 days to mature in a life span of 2-3 months, whereas, mice take 3 to 6 months to mature in a lifespan of 2-3 years. This rapid maturation of flies also results in experiments that gain results quicker and progress to further research more rapidly. When asked why fruit flies in particular of all insects to use, she admitted that “It happened by chance after Thomas Hunt Morgan over a hundred years ago developed the fly lab in the US from flies that were all over the place and easy to catch”. This ease of access and commonality of flies allows the research to be replicated, and is cost effective. 

To understand the specifics of the underlying cause of the disease, mutation experiments are undertaken. This is a process of changing the genetic code or DNA of flies to express the characteristic of a motor neuron disease. These are not done blindly but rather in conjunction with scientific literature and communication with collaborators and colleagues. There are multiple ways of introducing a mutation into DNA, and Dr. O’Sullivan utilised two main ways. She used gene knockdown which is the suppression of a gene of interest which is lost over generations but quick to introduce and allows the fly to grow to maturity to see what effect this missing gene had on the fly. A more permanent change which allows comparison with the wild type is gene knockout which she currently does using a protein called CRISPR - which allows a specific sequence of DNA to be identified and removed. This method increases the accuracy of mutagenesis (creation of mutations) and allows the results of the experiment to be analysed with a higher degree of certainty.

To see the results of a mutation experiment Dr. O’Sullivan introduces a visual tag during mutagenesis. This tag is a green dye that only shows up in the protein that has been created downstream of the mutation. In her research, together with her PhD students, they observe the motor neurons of the flies at a nano-scale and in-effect perform nano-surgery to extract the mutated motor neurons and analyse them. From the analysis, she saw that the mitochondria in the cells were not properly dividing leading to malformed proteins and lack of proper function that results in movement impairments.

Her lab like all others have been affected by COVID-19, however, unlike static labs she could not just leave her lab and work from home, as her lab contained living animals that needed to be maintained and fed. This meant that throughout lockdown she returned to her lab to tend to her animals and ensure that they too were kept well over lockdown. 

Her message was clear when I asked about the ethics of animal models, that it was essential to “understanding diseases that we have animal models”. She may have chosen flies to work on as they were the right organism for her research but there are many other animals out there that are also used. However, it is important that the right organism is used for the right research. It is always important to have a question and a focus when researching and to use all the tools at your disposal. She impresses that collaboration and sharing of knowledge in science is essential as it colours your own research by intertwining the ideas of others to compliment your own. 

Throughout this interview Dr. O’Sullivan’s passion for her research was always evident and heart-warming, as it showed the dedicated people who are working behind the scenes towards a better future.