Interview with Dr. Matthew Callow: Genomic sequencing was one of those real-world applications that utilized new molecular engineering strategies

Dr. Matthew Callow is Senior Director of Biochemistry at Complete Genomics. He received his PhD from the University of Western Australia in 1992 before post-doctoral research in Dr. Eddy Rubin’s lab at Lawrence Berkeley National Laboratory. His early research focused on lipoprotein metabolism using transgenic mice and expression microarrays. He then joined Callida Genomics Inc., and later Complete Genomics, developing sequencing technologies including DNA nanoballs and sequencing-by-ligation strategies. Since 2013, his work has advanced antibody-based sequencing-by-synthesis technologies including CoolMPS.

Q: Can you tell us more about yourself and what’s your work at Complete Genomics?

A: I am Senior Director of Biochemistry at Complete Genomics. I manage a team of four researchers developing sequencing chemistry for MGI DNA sequencers.

Q: Can you describe a typical day or daily routine at work? What are the major responsibilities of Biochemistry and why are they important?

A: We focus on achieving high-quality DNA sequencing with long reads of 1,000 bases or more. This requires high signal intensity from the target DNA nanoballs (DNBs), low background, minimal signal loss, and accurate loading of DNBs on flowcells. Our research explores the biochemical factors that affect these outcomes. Essentially, it’s about achieving high-purity, true-intensity base calls while reducing mixed signals that could lower quality.

Q: What is the most exciting or fascinating part of being a Biochemistry Scientist?

A: Understanding how biochemical systems really work and being able to manipulate them to achieve desired outcomes. It’s about identifying issues and solving them through technological innovation.

Q: What are the common challenges in your daily work and the most valuable lessons you’ve learned?

A: Designing good experiments is critical, so that you learn something meaningful, whether it’s expected or surprising.

Q: What are the most crucial qualities for being a Biochemistry Scientist, and do you have advice for aspiring scientists?

A: Be flexible and critical in your thinking. Let the data guide you to new hypotheses. Always ask why something is the way it is. Don’t accept results just because a machine or someone else says so. Consider the processes behind each result, ensure controls are in place, and ask whether the design or interpretation could be improved or if multiple conclusions exist.

Q: What first inspired your interest in genomic sequencing? Was there a specific moment when you realised this was your calling?

A: I’ve always been interested in applying science to real-world problems. Molecular biology suited my technological interests, allowing me to engineer systems to perform specific functions. Genomic sequencing was one of those applications that combined real-world impact with molecular engineering.

Q: You spent more than 15 years at Complete Genomics. Why did you join, and what has kept you there?

A: Moving from Callida Genomics to Complete Genomics was a natural progression, allowing us to develop DNBs and the entire sequencing process, including massively parallel ordered arrays of DNBs and generating sequence information. I’ve stayed because of the talented people I work with and their drive to advance the technology in novel ways.

Q: You’ve witnessed many important milestones at Complete Genomics. Which moment impressed you the most, and how did you feel at the time?

A: The early years of DNBSEQ™ development were particularly remarkable. So much innovation emerged from those first discoveries. Demonstrating multiple DNA sequencing chemistry strategies and antibodies binding rapidly, accurately, and reversibly were some of the highlights.

Q: What do you think are the most significant advances CG’s technologies can bring to biological research and people’s lives?

A: Low-cost DNA sequencing can deepen our understanding of biological systems and transform medicine by improving insights into therapies, treatments, and preventative care.