12 October 2023
Marie-Sophie Fabre is a Senior Research Officer in Dr Olivier Lamiable’s team in the Ronchese Laboratory. Her research aims to understand the changes that occur when immune cells encounter allergens, laying the foundations for understanding allergy development.
Marie-Sophie runs experiments to understand the role specialised immune cells called dendritic cells play in early allergy development. Equipped with tentacle-like arms, dendritic cells act as sentinels, roaming the body and sampling anything they come across – from potential threats like infectious viruses and bacteria, to harmless substances such as dust mites, pollen, or nuts.
Dendritic cells engulf and process these substances into smaller fragments called antigens. They then present these antigens on their surface using specialised structures called MHC (major histocompatibility complex) molecules, to be read by other immune cells, mainly T-cells. During this process, the immune system decides whether the substance is a threat.
“If deemed harmful, the immune system prepares the body to mount a rapid and powerful immune response against the threat,” says Marie-Sophie.
“After this initial confrontation, the antigen isn't forgotten – it's stored in the immune system's memory. This means that if the same antigen makes another appearance, the response will be even swifter and more potent.”
This mechanism proves highly effective against actual threats like viruses or bacteria. However, it becomes problematic when the initial substance marked as a threat is, in fact, harmless. In such cases, the immune system’s powerful response is triggered against something benign. This excessive immune reaction to a harmless substance is what happens during an allergy.
“This type of research into the most fundamental aspects of immune biology is incredibly important and paves the foundation of understanding that is needed before science is applied.”
“We’re aiming to decipher the extent to which dendritic cells influence the decision-making process, especially when determining if a benign substance should be treated as a threat, leading to allergies,” says Marie-Sophie.
Previous research showed a significant involvement of dendritic cells, but the exact mechanism remains shrouded in mystery.
“Which genes are turned on or off in the dendritic cell after it has captured the antigen? Do those modifications trigger changes that make them decide what sort of response they are going to trigger?”
“The interesting thing here, is that it seems to only be during allergic responses that this mechanism is unclear. In the case of anti-bacterial, anti-viral or anti-tumoral responses, the dendritic cells are instructing T-cells and telling them what to do. Those signals have been clearly identified. Yet, when it comes to allergies, we’re still in the dark.”
Marie-Sophie is trying to identify what changes occur in the dendritic cell during this process of early allergy development by deciphering the function of genes that are activated in dendritic cells.
“We’re hoping this will give us some insight into exactly which cellular signals are given by the dendritic cells that cause the allergies to develop,” she says.
“It’s painstaking work because we are switching off one gene at a time to see the effect it has on the process of allergy development.”
Specifically, Marie-Sophie is looking into a subset of dendritic cells which express a molecule on their surface called CD11b. This molecule is expressed at either high or low levels by dendritic cells in the skin.
“Data shows that it is the dendritic cells which have low levels of CD11b expression which seem to teach T-cells to mount allergic reactions. Low-CD11b dendritic cells are found in the skin which is interesting because our group have previously hypothesised that this is often the first site of allergy development.”
“The importance of fundamental research is often overlooked but what many people don’t realise is that to cure disease, first you must understand disease.”
Another avenue of research Marie-Sophie is exploring is the metabolic changes that occur in dendritic cells that have captured an allergen for sampling.
“We’ve observed there is a distinct change in metabolic activity once the dendritic cell captures a substance. We’re looking into characterising what these changes are,” she says.
“This type of research into the most fundamental aspects of immune biology is incredibly important and paves the foundation of understanding that is needed before science is applied.”
One of the problems in current-day research is that funding is often dependent on the justifying the research with potential applications. Though this seems logical, it doesn’t account for the fact that scientific advancement does not follow a straight line.
“Fundamental research can lead to unexpected discoveries that we often cannot predict the application of,” says Marie-Sophie.
“The importance of fundamental research is often overlooked but what many people don’t realise is that to cure disease, first you must understand disease.”
Basic research, like that conducted in the Ronchese Lab contributes to our understanding of processes such as genetics and cell signalling that can be applied to a wide range of research fields. It may even point to a pathway that can be used for developing treatments.
Marie-Sophie’s motivation for pursuing her research comes from the opportunity to learn and build knowledge.
“As long as I know more today than I did yesterday, I know I’m in the right career,” she says.
Marie-Sophie grew up on the outskirts of Paris and was the only one in her family who was interested in science.
“Everyone else in my family was more drawn to the humanities, but for me it’s always been science. I’ve wanted to be a scientist since I was 12 years old. Nothing really caught my attention like science did,” she says.
After going to university in Brittany, she came to New Zealand with her young family in 2011. Initially working with Professor Melanie McConnell at Te Herenga Waka – Victoria University of Wellington, she then moved to Professor Franca Ronchese’s lab six years ago.
“I feel like being a scientist has allowed me to stay in touch with my childlike curiosity where I’m exploring a fascinating new environment but on the scale of a cell.”