Daniel Levine

Project title

Interrogating Seasonal Temperature Signaling to the Clock

What is your project about?

Circadian clocks are biologically-encoded timing mechanisms that anticipate each new day. Biologists have learned a great deal about the role of the clock in orchestrating a suite of physiological processes by studying it in idealized environments where temperature is kept comfortable, and day and night periods are each set to 12 hours. Yet, these are not the environmental conditions that clocks evolved under. In nature, the average environmental temperature and the daily duration of the day and night change throughout the seasons, and yet we have very little mechanistic insight into how the clock learns what season it is and how it adapts daily patterns in behavior and metabolism to synchronize with the season. Here, I will interrogate the mechanisms – and metabolic outputs – wherein the clock integrates these seasonal environmental conditions.

How did you become interested in your particular field of research?

I have always been interested in molecular metabolism and its role in regulating the conversion of DNA into RNA (transcription). When I was in graduate school, I learned about the circadian clock by rotating with Joe Bass and immediately became hooked by the elegant sinusoidal patterns that it generates in so many physiological processes. During my PhD, I worked on characterizing metabolic inputs into the circadian timing system, but, while doing so, was always puzzled by the big picture of it all: why is the circadian clock integrating metabolism at all? Would that not be better suited to the myriad other biological pathways that we already know perform that function? Years of pondering this fundamental question made me realize that seasonal changes in the daily environment must have been an evolutionary influence on the clock. So, I set out to test it.

What are the scientific challenges and perspectives in your project?

A major challenge is that most people can immediately think of organisms that readily adapt their biology to the seasons. Polar bears hibernate in the winter. Reindeer ‘eat’ 24-hours a day during the summer. But humans (and mice) do not have similarly obvious and extreme adaptations to the seasons, so our natural biases cause us to assume these organisms do not adapt at all. Yet, perhaps humans (and mice) adapt in a more insidious way? It is my goal to leverage the powerful genetics, molecular biology, and physiology of the mouse experimental system to understand these more subtle adaptations to the seasons so that we may better appreciate how humans adapt, and how conveniences in our modern societies may be co-opting this evolutionarily ancient signaling pathway to contribute to some of the common pathologies that pervade our society.

What is your estimate of the impact, which your project may have to society in the long term?

My project explores the impact of environmental temperature on the way that the biological circadian clock interprets time. I posit that high daily temperatures tell our internal clocks that it is the summer (and low temperatures, the winter), and that the mechanistic signaling pathway that underlies this phenomenon is responsible for driving organism-wide changes in metabolism. In the near-term, it is my hope that this project will suggest methods that people can adopt in their day-to-day lives to potentially improve their metabolic health. In the long-term, it will define specific molecular events that are responsible for conferring seasonality and open the door for designing a novel class of therapeutics that target them.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

The Sapere Aude grant gives me the outside funding to establish my own laboratory at the University of Copenhagen and fully develop a research program in seasonality and the circadian clock. The opportunities for professional development and networking that are provided through the Sapere Aude grant will help me feel grounded and a part of a community as I start a new chapter of my research career in Denmark. The proposed research will not only provide answers to exciting questions, but are likely to generate novel insight that will continue to propel my lab forward into the future.