ECR Spotlight – Till Harter

Till Harter

Describe your scientific journey and your current research focus

I started my career from a more applied perspective, obtaining a BSc in Agriculture in Germany and an MSc in Aquaculture and Fisheries in The Netherlands. However, I always found myself gravitating towards the mechanistic physiology aspects of my work. My MSc project at Wageningen University was based on a previous study by Carol Bucking and Chris Wood, who studied the digestive physiology of rainbow trout. After my MSc, I decided to contact Chris at McMaster University in Canada to explore the option of doing a PhD in his lab. Due to a lack of funding for international students, he re-directed me to Colin Brauner at the University of British Columbia. I don't think I ever thanked Chris for this suggestion, but Colin turned out to be the best PhD advisor I could have hoped for. Working in Colin's lab cemented my interests in cardiovascular physiology and gave me the tools to pursue my own research interests on comparative red blood cell physiology. I then moved to San Diego, where I did a 4-year postdoc with Martin Tresguerres at the Scripps Institution of Oceanography, focusing on the cellular physiology of fish red blood cells, which resulted in this paper (among others).

How would you explain the main finding of your paper to a member of the public?

Carbonic anhydrase is an enzyme that helps animals breathe out carbon dioxide, a gas produced as a byproduct of metabolism. Not surprisingly, carbonic anhydrase is abundant at the lungs or at the gills of most vertebrates, where it comes in contact with the blood. However, the bony fishes are a notable exception and, for reasons that we don't fully understand, lack this type of carbonic anhydrase at their gills. The prevailing hypothesis predicted that carbonic anhydrase at the gills of bony fishes would interfere with a specialized mechanism of red blood cell pH regulation that protects oxygen transport. With my colleagues at the Scripps Institution of Oceanography, we set out to test this idea, and were surprised to find that it doesn't stand up to scrutiny. Our data showed that carbonic anhydrase does not interfere with red blood cell pH regulation and should not affect oxygen transport in vivo. Why bony fishes have lost carbonic anhydrase at the gills is still unknown, but clearly, other hypotheses must be considered to explain the evolutionary loss of the enzyme at their gills.

What are the potential implications of this finding for your field of research, and is there anything that you learned during this study that you wish you had known sooner?

Until now, we assumed that carbonic anhydrase at the gills of bony fishes was lost when they evolved a unique mode of oxygen transport in the blood that requires regulating red blood cell pH. However, in light of our recent findings, we must re-consider the sequence of evolutionary events that have led to the unique cardio-respiratory physiology of today's bony fishes, a vast group that represents half of all vertebrates.

Which part of this research project was the most rewarding/challenging?

I think the surprising results of our study were both the greatest challenge and reward. It was challenging because it forced us to re-think what we thought we knew about the complex oxygen transport system of bony fishes. However, it is also rewarding to do away with some of our previous misconceptions and thereby advance our understanding of the physiology of a very diverse group of animals.

Are there any important historical papers from your field that have been published in JEB? If so, which paper, and how did it pave the way for later research?

This is a difficult question to answer because there are many. Much of the early work on gill function and gas exchange in fishes was published in JEB in the 1960s and 1970s, with historical papers by Hughes, Randall, Cameron and others. However, the one paper I keep coming back to is Kiceniuk and Jones (1977), ‘The oxygen transport system in trout (Salmo gairdneri) during sustained exercise’ (doi:10.1242/jeb.69.1.247). Their study provided the first comprehensive dataset on arterial and venous gas and acid–base measurements during graded exercise in the rainbow trout, and really opened the door for further mechanistic studies on cardiovascular physiology in fish.

Are there any modern-day JEB papers that you think will be the classic papers of 2123? If so, which paper, and how will it pave the way for future research?

One of the JEB papers that has been very influential for my scientific career was the 2006 study by Carol Bucking and Chris Wood on water balance during digestion in fish (‘Water dynamics in the digestive tract of the freshwater rainbow trout during the processing of a single meal’, doi:10.1242/jeb.02205). Their study revealed the complex interactions between osmoregulation and digestive physiology in freshwater fishes and was the basis for my own MSc project that ultimately led to me pursuing a career in physiology. I could easily see this JEB paper becoming a 2123 classic!

What do you think experimental biology will look like 50 years from now?

I suspect that, if current trends continue, there will be an increased focus on research addressing the impacts of anthropogenic environmental change on wildlife, agricultural species and human health. The use of novel -omics techniques has accelerated the pace of discovery, but has also led to a decline in interest and funding for traditional organismal and cell physiology. My hope is that there will be a reckoning that, while -omics approaches are important tools to generate hypotheses, there is a dire need for functional and mechanistic work to test these ideas. Therefore, only a truly integrative approach to biological research will allow us to make significant advances in this field.

If you had unlimited funding, what question in your research field would you most like to address?

I would set up a comparative red blood cell physiology group to study how red blood cells mediate the fine balance between oxygen supply and demand. We already have indications that red blood cells can sense the conditions in the microvasculature and produce signaling molecules that regulate blood flow and mitochondrial respiration. However, what cellular mechanism are involved and how they might be impacted by environmental change in some animals or by disease in humans is still largely unknown.

What changes do you think could improve the lives of early-career researchers, and what would make you want to continue in a research career?

Being an ECR is tough! Low wages for grad students and postdocs have not kept up with the cost of living, and short-term contracts, frequent moves and much uncertainty take their toll on family planning and mental health. Every year, academia loses many talented ECRs due to the exploitative work environment it fosters. Fixing the issue is not trivial, but will require a fundamental rethinking of how we, as a society, view and value the roles of academics in research and teaching. But ultimately, those in positions of power (politics, funding agencies, university officials and PIs) have a disproportionate responsibility to improve conditions for future generations of academics.

What's next for you?

I'm currently enjoying my research on high-altitude adaptations in the red blood cells of deer mice, at McMaster University in Canada. But, like most postdocs, I am eagerly trying to secure a tenure-track faculty position. I've recently received funding from the German Science Foundation (DFG) to start my own research group on comparative red blood cell physiology in Germany, and we are in the process of determining if and when we'll be ready for the next big move.