Lawrence Kazak: a scientific journey of focus and refinement

This article was taken from a special feature in Nature Metabolism where Dr Lawrence Kazak reflects on the journey that led him to become a researcher.

My interest in molecular metabolism and mitochondrial biology stems from when I first learned that genes are responsible for the training benefits of exercise. My scientific career path was not straightforward. As a young boy, I spent a lot of time cataloguing plants during walks with my grandmother. I loved chemistry in the first years of high school; however, the science education I received at that time was subpar. In contrast, the fine-arts program at secondary school was incredibly strong, with dedicated teachers who took pride in their work. After high school, I pursued fine arts and simultaneously began training in Brazilian martial arts for the next 8 years. It was during that time that I realized I still had a passion for science but had never had the encouragement that I needed when I was younger to give me the confidence to pursue it. Despite this, with a ‘toe in the door’ in martial arts, I began my scientific career by studying exercise physiology, during which I developed a love for mitochondrial biology. I quickly understood that I needed to attain proficiency in biochemistry and molecular biology. So I undertook PhD studies at the Mitochondrial Biology Unit at the University of Cambridge, where I worked on DNA replication and protein trafficking in mitochondria, under the supervision of Ian J. Holt, who was the first to identify a connection between deletions in mitochondrial DNA and human myopathy, in the late 1980s.

My personality is such that I dive deeply with both feet so that I can be fully engaged with my interests, and because of this, I felt it was time to stop my martial-arts career and devote 100% of my time to the scientific pursuit. In retrospect, I don’t have regrets about that decision, as my participation in martial arts was a critical step that brought me back to a path based in science.

My parents emigrated from the USSR in the late 1970s and worked multiple jobs to make ends meet. Like any parents, they loved and supported me as I grew up, but because they were always working, they were unable to provide me with the formal guidance or mentorship toward intellectual pursuits that some kids receive on their path toward a scientific career. I had to piece a lot of this together on my own, and, looking back, I see that I would have benefited from more scientific guidance and encouragement during times when I struggled with some concepts. My journey has affected my approach toward mentoring my trainees for the better. Encouragement during this critical time in a trainee’s life is paramount for their future careers, and I try to be aware of when trainees are struggling and to provide motivation and encouragement when they need it.

For my postdoctoral work, I joined the lab of Bruce Spiegelman at Harvard Medical School, where I continued to work on mitochondrial biology, but with a focus on adipose tissue and bioenergetics. The work in my own lab is a direct extension of the research I started there. The Spiegelman lab was a great environment, and I learned a lot about myself as a person and the type of scientist I wanted to be. Most importantly, I learned the importance of focusing on one problem at a time and trying to solve it to the highest molecular resolution of my ability. Detailed focus on a biological problem does not make for myopic research. On the contrary, a diversity of scientific outgrowth appears naturally as you dive deep, provided, of course, that you are not dogmatic in your thinking. A single manuscript cannot contain an entire body of work. However, a multitude of papers, each building upon the findings of the previous ones, is a style of science that I have found to be incredibly satisfying and an approach that my trainees also appear to take satisfaction in.

Of course, this style of science does not suit everyone’s taste; the style of science that investigators pursue will be heavily influenced by their funding environment and available resources, and the capabilities of their trainees. After a move to a new city or institute, it takes time to familiarize oneself with the local research network and the collaborative opportunities available. Once settled in, with more resources and funding secured and a familiarity with the local research community, one can cast a wider scientific net and take on riskier projects. Therefore, considering all these distinct variables, I have personally found it beneficial, and maybe even necessary, to focus the scope of my research program early on, starting slow and gradually spreading out to different areas of biology.

I started my lab in 2018 with one research assistant and one trainee. Currently, my lab hovers between four and six people, and most trainees work on some aspect of the same pathway. In 2019, the first major paper that came out of our lab, on creatine transport in thermogenic adipocytes and obesity, was published in Nature Metabolism (L. Kazak et al. Nat Metab 1, 360–370; 2019). This paper was incredibly important because it gave the lab a good start within the first year. No doubt, it played important roles in speaker invitations to conferences, grant success and stimulating a high calibre of trainees applying to my lab.

New research areas in the lab can be traced back to our starting point: creatine biology in thermogenic adipose tissue. This type of focus has been successful for us so far, because although all trainees have independent research projects, there is room for synergy if they choose. This approach has also benefited troubleshooting in the lab and has catalysed scientific partnerships within the lab. My advice for late-stage postdocs or early faculty is to choose a biological problem that is important to you and to focus on solving one problem at a time. I would strongly advise against spreading yourself thinly, especially at the start of your career. In my experience, to obtain grants, the community needs to see that you can take a problem and solve it, and to do this well, you need to focus.

 

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