Take 10 with... Denis Nyaga

1.  Describe your research topic to us in 10 words or less.

I investigate the genetics of rare disorders.

2.  Now describe it in everyday terms!

In New Zealand, around 150,000 children have rare diseases. Unfortunately, less than half are diagnosed before their first birthday, and nearly a quarter wait over a decade for a diagnosis. That is where my work with the Newborn Genomics Programme comes in. We focus on critically ill babies in neonatal and paediatric intensive care units (NICUs and PICUs). We sequence their DNA, along with their parents', to hunt for genetic clues that might explain their illnesses. Our goal is to provide answers and speed up the diagnosis process for these families.

3.  What are some of the day-to-day research activities you carry out?

My typical day is a balancing act! I dive into the latest research papers, fine-tune our genetic analysis pipelines, and develop new methods to process genomic data. On top of that, I also supervise PhD students. It is a thrilling challenge that keeps me on my toes, ensuring I stay up-to-date with the latest breakthroughs while mentoring the next generation of researchers.

4.  What do you enjoy most about your research?

The Newborn Genomics Project is exciting. We provide essential genetic information to doctors and families to treat over 400 rare diseases with available treatments. Take this one condition, for example; some kids are born with a genetic condition that causes an amino acid called phenylalanine to build up in their bodies. If we diagnose it early and start treatment right after birth, we can prevent severe brain and nervous system problems. The treatment involves a special diet that eliminates certain proteins and includes supplements without phenylalanine. It is amazing how a quick diagnosis can make a huge difference in these kids’ lives.

5.  Tell us something that has surprised or amused you in the course of your research.

One thing that always surprises me is how unique each person's genome is. Every new case presents something unexpected, like solving a new puzzle every day. What is really amusing is how quickly our field evolves. I might spend weeks mastering a new technique or tool, only to have something newer emerge a month later. It definitely keeps us on our toes!

6.  How have you approached any challenges you’ve faced in your research

I tackle research challenges with a mix of collaboration and persistence. One major hurdle is the volume and complexity of genomic data. To address this, I constantly seek out new computational methods and tools, attending workshops and conferences to stay current in bioinformatics. When I hit a roadblock, I reach out to colleagues for fresh perspectives. Another challenge is making our findings actionable for clinicians. We work closely with doctors and geneticists to understand their needs, which helps in refining our reports to be more accessible and valuable in a clinical setting. Finally, I have learned the importance of resilience. Not everything works out as planned in research, and that's okay. I view setbacks as learning opportunities and use them to improve our workflows in the future.

7.  What questions have emerged as a result?

Several intriguing questions have emerged as we have delved deeper into our research. How can we streamline genomic analysis to provide faster diagnoses for critically ill newborns? Every hour counts in the NICU, so we seek ways to speed up our process without sacrificing accuracy. How should we handle incidental findings – genetic variants unrelated to the baby's current condition but potentially important for their future health? What about variants of uncertain significance? These genetic changes are a constant puzzle, and we are exploring ways to classify them more accurately. Finally, what role might epigenetics play in these rare disorders? We are investigating whether factors beyond the genetic sequence can explain the onset of these rare disorders.

8.  What impact is your research having or what impact do you hope it will have?

Our research is already having a significant impact by providing rapid genetic diagnoses for critically ill newborns, enabling doctors to start life-saving treatments early. Beyond immediate benefits, our genetic findings are helping families make informed decisions about future pregnancies. Looking ahead, we aim to shorten the long, frustrating diagnostic journey for many kids with rare diseases. Additionally, we hope our work will influence public health policies, particularly in newborn screening and genetic testing.

9.  If you collaborate across the University, or outside the University, who do you work with and how does it benefit your research?

Our research thrives on collaboration, both within and outside the University. Internally, we work closely with the Liggins Institute Analytical Platform. Externally, we have strong ties with genetic counsellors, clinical geneticists, metabolic specialists, and paediatricians for Newborn Services at Te Whatu Ora (Health New Zealand). We also collaborate with the Victorian Clinical Genetics Services (VCGS) in Australia, broadening our perspective and contributing to global advancements in genomic research.

A key aspect of our work involves Māori co-governance. We partner with Māori health organizations and iwi representatives to ensure our research respects and incorporates Māori cultural values and health perspectives. This collaboration is crucial for making our genomic research culturally appropriate and beneficial for all New Zealanders.

10.  What one piece of advice would you give your younger, less experienced research self?

Take opportunities as they come. The research field is dynamic and often unpredictable, so it is important to be open to new possibilities and challenges. Seizing opportunities, even if they seem daunting or slightly off your planned path, can lead to unexpected breakthroughs, valuable collaborations, and personal growth as a researcher. And as my boss, Prof Justin O’Sullivan, always says, 'Remember to have fun as you only get to do this once.'