This month we’d like to introduce Dr Hamish King, Lab Head at The Walter and Eliza Hall Institute of Medical Research.

Hamish will be speaking at our online Epigenetics seminar on 21st April.  He has also taken the time recently to tell us a little about his career journey, his research and himself.

We hope you enjoy learning about Hamish as much as we did.

What brought you to the world of epigenetics, epigenomics and B cells? How did it all begin for you?
I grew up in rural South Australia, and I was fascinated with the natural world from a young age. I naturally gravitated towards studying biology at university where I was particularly interested in molecular biology and DNA. I remember being blown away by lectures on subjects like genetic imprinting, microRNAs and the histone code – how do our cells control such complex processes? This was only the beginning, as I then went to the University of Oxford to do a PhD and learn more about the gene regulatory functions of chromatin-modifying complexes in mouse embryonic stem cells with Prof Rob Klose.
Marnie Blewitt
For my postdoctoral work, I wanted to apply the same genome-wide questions and approaches I had used in my PhD to the human immune system. I decided to train and develop expertise in human B cell immunology with Dr Louisa James (QMUL), focusing on how antibody class influences B cell fate and function during maturation in the germinal centre reaction. This fascinating process is required to generate immune memory, and epigenetic dysregulation in this process is known to contribute to autoimmune disease and cancer – so it felt like a natural fit to work in this area. Recently moved back to Australia, I am now looking forward to combining these two arms of my career – epigenetics and immunology – into some exciting new research.

Can you tell us about a couple of things happening in the King Lab right now that you’re excited about?

One of the projects I am most excited about is following up from a recent paper where we found that non-coding genetic variants associated with different autoimmune diseases show highly cell type-specific chromatin accessibility in a particular stage of B cell development – the germinal centre. We are going to be using the latest ex vivo human B cell culture systems and CRISPR/Cas9 (epi)genome editing to understand more about how these genetic changes disrupt normal B cell gene regulation and function. From this previous study, we also have identified several apparently immune-specific chromatin pathways, some of which their mechanism of gene regulation is very poorly understood.

I am actively looking for motivated scientists at all levels to join the team and help with these exciting projects – so do get in touch if you are interested!

Would you like to tell us a little about WEHI?

The Walter and Eliza Hall Institute was established in 1915, and is Australia’s oldest medical research institute. My lab is in the Epigenetics and Development division, where we have some fantastic researchers studying gene regulation in neurodevelopment, haematopoiesis, embryology and cancer, to name just a few examples. One of the strengths of the WEHI in my opinion is the strongly collaborative atmosphere that exists – the ability for epigenetics researchers to work closely with immunologists or neuroscientists for example and share expertise and techniques.

If funding and time were unlimited, what dream idea or project would you like to develop?

In one sense, I feel like we are setting out to tackle my dream project – how does genetic and transcriptional dysregulation cause autoimmune disease? From our previous work, we know that we need to ask this question in the right cellular context, so a key challenge is the need to do this in primary human germinal centre cells. For example, we can’t understand the function of non-coding genetic variants, typically found in enhancer regions of the genome, in mouse models as they are not conserved. Cell lines, although incredibly useful, also have significant limitations given that gene regulation is so highly context specific. So one of the long term goals for the lab is to develop better models to interrogate primary human immune cells. One challenge working in human immunology is accessing the right cells at the right time. Steady state cells circulating in the blood can tell us some information, but exist in a really different state to activated or differentiating cells in many potential tissue contexts. Single-cell genomic atlas studies are providing more and more resolution in this area, but in the long term we need to be layer on functional interrogation of gene regulatory networks across diverse immunological and developmental settings to make progress in understanding the cause of immune disease.

Outside your own lab, what research or technological developments in the field are you excited about?

The rapid rise and development of single-cell genomics in recent years has led to increasingly large datasets mapping different cell states and types. There is a lot to be learned from these descriptive studies that often can’t be summarised in the typical journal article format, so I am excited to see how these resources are used to discover and test new hypotheses. I’m also looking forward to a transition in the single-cell field to include more functional readouts, like CRISPR/Cas9-interference or activation assays to experimentally test gene function or regulation in highthroughput.

How important has collaboration been to your research and your career?

In my opinion, collaboration is one of the most important skills we must have as scientists. Every working relationship in the lab environment is a collaboration – between student and supervisor, core facility staff and post-docs, and all other combinations. Being able to work well and support others is not just important to achieve the best research outcomes, but is also a lot of fun! Collaboration has been absolutely pivotal during my career, and it is one of the most rewarding parts of the job to be able share ideas and technical expertise.

In your career to date, of what are you most proud?

I found this a really difficult question to answer, and maybe it is for a lot of scientists, as we are trained to always be looking forward to the next question or problem that needs to be solved. Rather than any particular achievement or publication, I would have to say I am proud of taking risks, trusting my gut to follow my curiosity – a couple of times in my career I turned down opportunities that weren’t quite what I wanted to study or work on so that I could pursue what I really wanted. Sometimes these decisions were easy, sometimes they were hard, but I’m very glad I took the risks regardless.

Can you give us one piece of advice for early career biomedical researchers?

One of the best bits of advice I can give is how important it is to find supportive mentors throughout your career who will help your development – they honestly make all the difference. I’ve been fortunate to have the support of some fantastic scientists who are also generous and kind people (those traits don’t always go together!). On a slightly related point, I think it’s also really important to remember to keep a healthy work-life balance and perspective about your career. Often in academia we are told we must be prepared to work crazy hours because we are privileged to be conducting research and doing something we love. But as a creative endeavour, we can’t perform the best science when we’re burnt out, so learn to recognise how you work most effectively and make sure there is time for yourself when you need it.

How are you enjoying being back in Australia after many years in the UK?

I had a fantastic time in the UK, but after nearly a decade there and a tough few years during the pandemic it was a big relief to return to Australia. While I will miss the ease of travel to Europe and other parts of the world, I really enjoying exploring Melbourne and Victoria.

Outside of work, what do you like to do?

One of my favourite ways to relax is by spending an afternoon pottering around in the kitchen, cooking for friends or family. A particular favourite to make from scratch are Chinese potsticker dumplings. I have also recently taken up pottery, which has been a challenging but rewarding hobby to develop.