Immunologists are leveraging state-of-the-art CRISPR technology to identify which genes cause allergic responses.
In the developed world, a fresh problem has emerged alongside the drive for germ-free homes and standardised vaccines in recent years – strong allergies.
Now scientists, among them immunology PhD student Aydan Szeto (Croucher Scholarship 2016) at the University of Cambridge, are trying to discover the triggers for such responses and how to dampen them.
Immunology is broadly divided into two type of research: the first (Type 1) focuses on how bodies fight intercellular threats; the second (Type 2) seeks to combat extracellular parasites.
Many researchers exploring Type 2 issues have previously concentrated on the role of Type 2 immunity in the protection against parasitic helminths. However, it has also become clear that too much cleanliness can lead to other problems.
“One hypothesis is that we needed immunity in the past, but as humans evolved, they moved into more sheltered environments where we are no longer exposed to these pathogens,’’ Szeto said. “Now, we need pathogens to keep the immune system in check. Evolutionarily speaking, our bodies are not used to a pathogen-free environment.”
Allergies are often regional and can be triggered by diverse allergens – for instance a peanut butter allergy is common in North America, but rare in Asia. “The key is identifying the common pathways responsible for initiating these reactions,” Szeto said.
In the human body, lymphocytes, a type of white blood cell, orchestrate the response given to new pathogens, based on signals from other cells about the nature of the pathogen. Szeto is working to identify the reasons why certain responses are prompted.
To do this, he is using cutting-edge CRISPR screening technology to examine the mouse genome, for which all 20,000 genes have been mapped, systematically knocking out genes to see if the response is dampened.
After a year of screening, Szeto has found 10 possible hits. Over the next year, as he finishes his doctoral thesis, he will further research how these genes influence the response driven by lymphocytes.
Understanding the molecular regulators involved in initiating immune responses may present novel targets for manipulating such reactions.
The broader goal of studying Type 2 immunity is to understand how the human body orchestrates a response to assist clinical applications, for example, where cells could be removed from a patient, edited externally, then returned to the body.
However, Szeto estimates it may take 10 years or more for such somatic (body) cell gene editing to be publicly available. Alternatively, we may already have existing drugs to target novel regulators identified in this work.
Indeed, one of the reasons that Szeto enjoys studying immunology is because it reveals how little we know about the human system.
In the past, people thought a cleaner environment would make them less susceptible to disease. Instead, it now appears to be having an ill-effect of its own, by dysregulating the immune system and making it oversensitive.
Like many aspects of life, immunology is all about “creating a balance”, Szeto said.
Aydan Szeto obtained his BA in Biochemistry from the University of Cambridge. His final year thesis involved working under the supervision of Dr Darerca Owen on a study of the thermodynamics of the Cdc42-WASP interacting interface. He is now applying his skills and knowledge to research in immunology as a PhD student in the MRC Laboratory of Molecular Biology, University of Cambridge. Szeto received his Croucher Scholarship in 2016.