The Woolcock Institute of Medical Research

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Sex, the Y chromosome and lung disease

Wednesday, October 06, 2021

An important factor that distinguishes half the global population from the other half is hugely understudied: sex. Woolcock PhD student Diren Reddy explains.

Don't worry, I'm not about to have an awkward talk about the birds and the bees; I'm talking about biological sex differences between males and females in disease.

Sex, gender and chromosomes

First, let's get our definitions straight.

Biological sex – as in males and females – refers to the sex chromosome pairing. Males have an X chromosome with a Y chromosome, while females have two X chromosomes.

Gender – as in boys and girls – refers to the social characteristics that we ascribe to an individual.

My PhD investigates the biological sex differences between males and females in disease.

Biological sex and disease

Sex differences are incredibly prevalent across almost all organ systems and diseases.

For example, when I investigated the effect of cigarette smoking, I observed a very interesting pattern: when mothers smoke during pregnancy, we see a higher risk for a range of diseases in male offspring; however, when looking at adult cigarette smoking, we see a reversal of this trend towards a higher risk in females.

This difference is particularly prevalent in asthma, a chronic inflammatory disease of the lungs that affects almost 11 percent of the Australian population. Male children demonstrate a high number of cases of asthma. However, post-puberty we see this reversal again towards an increased number of cases in females. 

When I saw this in my research, I realised that there is a complex balance between sex and disease.

Sex differences and asthma

My PhD aims to uncover the causes for sex differences in a person's susceptibility to asthma, and the severity of their asthma.

The Y chromosome is commonly disregarded and just considered a genetic wasteland, with much of the focus on the X chromosome.

The Y chromosome is smaller and contains fewer genes. However, I believe that this chromosome is where the imbalance in asthma susceptibility and severity lies between males and females. Females can't produce genes on the Y chromosome because they don't have one, and a growing body of work shows that these genes contribute to critical biological processes.

In my research I've used the revolutionary tool CRISPR CAS9 to modify the Y chromosome and investigate how it contributes to critical disease processes in asthma.

My PhD is the first thorough characterisation of the Y chromosome in asthma. My results have already shown that these genes contribute to important cellular functions. They show that there is a dramatic change in the inflammatory response as well as a dysregulation of factors that can alter the structure of the airways. These are hallmark features of asthma and contribute to worse disease outcomes for patients.

What I hope to achieve

Modern medicine is more and more focused on designing individual, personalised treatments. 

My research highlights that the Y chromosome needs to be considered when investigating disease mechanisms and processes. By increasing our understanding of the Y chromosome, I hope we will be able to develop better and more potent treatments for asthma, COPD and other lung diseases.

About Diren

Diren Reddy is a PhD student in the Respiratory Cellular and Molecular Biology Group at the Woolcock Institute of Medical research and the Respiratory Bioinformatics and Molecular Biology group at UTS.

Diren's research investigates novel pathways that cause differences between males and females in lung disease. In particular, he's interested in the inherent genetic and epigenetic factors that drive a difference in disease severity and progression, using a range of molecular biology techniques from genetic engineering to proteomics analysis.

Diren's supervisors are Professor Brian Oliver, Dr Alen Faiz (UTS) and Dr Jeremy Chan (UTS).

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