Interview With Bharath A.

Thanks so much for joining us this morning! Could you tell us a little bit about yourself and your research interests?

I am currently a theoretical and computational chronobiologist. I work in the area of circadian clocks. My PhD was in the field of wireless communications with a focus on designing new technology to provide higher rates of data transfer between phones and data stations. In a sense, cellular technology and chronobiology are connected because your cellphone’s functions depend heavily on oscillators. There is a lot to do with oscillators, amplitude, and phases, which transitions into circadian clocks and circadian rhythms. After completing my PhD in electrical engineering in the US, I relocated to Germany and explored my interest in biology, ultimately combining my knowledge of biology and engineering at a theoretical biology institute. Now, I have my one small group here at Humboldt University in Berlin.

You’ve done a lot—from blood tests for circadian rhythms to pure modeling work. What is the direction you’re most excited about in your current research? 

I am most interested in circadian medicine, (or chronomedicine). We began looking at how rhythms were generated, starting with the negative feedback loop, which was awarded the Nobel prize in 2017. In the late ‘90s and early 2000s, all the clock genes were found, and then we moved into using kinds of massive sequencing technology. We started to look at initial clock outputs, which include all the transcriptomes, and peripheral clocks in all the different tissues.

Through proteomics and metabolomics, we now have a very good idea of how rhythms and clock outputs are generated. We have also started looking at how these outputs couple with different physiological processes and how they mediate the interaction between clocks, immunity, metabolism etc. It really does seem to affect almost everything. So, I think the next natural step is to look at how we can leverage this understanding to help people improve their health. I am taking the more computational and theoretical angle, including blood tests, towards improving people’s health through circadian medicine. 

I am also involved in clinical studies that explore what has already been done in mice, although human clocks, of course, are more heterogeneous. I tend to focus on the molecular outputs of the human clock. We are trying to map out how different clocks look in peripheral tissues of specific patient groups or subpopulations. We are also currently trying to associate these data with other clinical parameters. 

I started at Arcascope about a year ago, and that’s when I learned about circadian rhythms and how it affects you day-to-day. I’m still learning, but I find the field of chronomedicine very exciting. 

What we are talking about is cutting edge in terms of medication. Even simple things, such as timing—whether to consume medicine during the day or night—have a huge impact. For example, my colleagues discovered this in a patient’s case of rheumatoid arthritis. 

The symptoms of rheumatoid arthritis are strongest early in the morning, with certain markers ascending really early in the morning, around 4:00 or 5:00 AM. So they took the standard medication, formulated a delayed-release form, and asked patients to take it at night so that the medication was released when the disease symptoms were at their highest rate. It was a very, very simple chrono-solution. I think it was published in Lancet, around eight or ten years ago in the early days of chronomedicine. Some very simple things, such as timing medication, can improve the efficacy of medicines that already exist. 

How has your work on biological rhythms changed the way you live your life day to day?

I will divide this into two parts of my life: before kids and after kids. After having kids and experiencing the coronavirus pandemic, things have become more chaotic. I have always had a fairly regular circadian lifestyle. Most of my life, I could survive with maybe six or seven hours of regular-quality sleep. I would go to bed at 9:00 PM and wake up at around 5:30 AM. And only after University, I started staying up later, typically going to bed at 11:00 PM and waking up in the morning around 6:00 AM.

I never slept in much because I was always awake once the sun was out. And now with kids, I try to work when they are asleep. So I end up staying up a lot later than I should. I know that I should not eat at night, but I still do it even though I know it’s wrong, so I will try to change that.

In fact, the funny thing was that after we created this blood test, we did the blood test on ourselves. At the time when my son was an infant, we had really crazy sleep/wake schedules. Still, when I did the blood test to determine my chronotype, it was actually the most consistent measurement of all the people we had tested. We tested at three different days and my chronotype estimate was within ten minutes of each other. So, objectively my chronotype looks pretty stable in spite of changing seasons and having to endure a crazy sleep/wake schedule.

Olivia, Arcascope’s CEO, is actually working on a blog post about how sleep regularity could be more important than sleep duration. 

Yes, possibly. As a chronologist, we do not really know how long it takes before one starts feeling the negative effects of an irregular sleep schedule. At the moment, I’m not living a chronologically good lifestyle based on what we know. At a recent meeting, we had a discussion on the effects of living against your clock and it is still unclear. 

So we talk about correlations, which is all we have. We do not really know whether it’s a consequence, which way the causality goes or whether it is bidirectional. So, it is hard to say. Essentially if we change the balance, we change the likelihood that something can go wrong.

For example, Satchin Panda, the author of The Circadian Code, discusses fasting, and emphasizes that a 12-hour fasting period at night is very important. That is one very simple takeaway from his work. I tried fasting for the longest time but it is hard, especially if you stay up quite late after dinner, then it’s hard to fast. I realize my kids can fast because they end up sleeping for 12 hours. Although, I personally know scientists in his lab who have been regularly fasting for quite some time.

And that’s an interesting thought too, is if you do eat outside of your optimal meal window, what exactly does that do?

At this point, we do not know. I do know about [timing and] caloric restriction from Joe Takahashi. It is not just about when you eat, but also how much you eat. Also, if you have a long fasting window, you probably eat less throughout the day; on average, you eat less if you have a longer fasting period. This means that for the larger part of your wake time you are not eating.

As the former public outreach fellow for SRBR, what did you learn from the experience?

The biggest takeaway is that this field, initially narrow, is now really broad. We focus on how our rhythms are generated and the outputs of the clock. Now, since we are at the point where we are looking at interactions with other systems, you can pick any other aspect of physiology and apply a clock angle. There are people working on that interface, looking at immune clocks, microbiome clocks, cancer clocks, metabolism clocks and endocrinology clocks. 

From a personal perspective, I think that this broad field is challenging because I am not a biologist with the background information that one needs to understand a lot of this. I have to know about clocks, but I have to understand some background in these other fields as well, and being in this position forced me to keep abreast of everything in these interfaces.

Through networking, I met a lot of people. I was the fellow at the beginning of the coronavirus pandemic, so I was networking while everything was digital, including our SRBR conference, which was hosted online in 2020.

It was actually surprising, people didn’t really have any baseline ideas about how this was going to work. And it worked quite well. At that point, people were quite wired and they were kind of happy to put up with anything to still function in the sciences.

One of the rewarding things, which I found out after the fact, is that a lot of people found the content produced from SRBR, which helped people create or maintain some sort of connection with the outside world since they could not travel to meetings. Everybody was more active; there were a lot of PhD students and postdocs.

How do you think we can communicate our results better as a field in general?

This is something that is close to my heart. As an SRBR public outreach fellow, my true goal was to do public outreach, although we also did a lot of “in-reach”. We did a lot of outreach within the chrono-community, which is important to other scientists who are less aware of chronobiology, similar to when you entered the industry and you were less aware of how much clocks impact other fields. 

One example was the Daylight Savings Time (DST) laws during my time as the public outreach fellow. We had a town hall and still, in spite of so much science being out there, we did not get the result that we wanted. In a sense, we got the exact opposite result. Of course, that is not purely because of the science, but communicating science is also important from that perspective. As scientists, communication is also important, since the science must be seen in the context of lifestyle, society and general health. I think we have to become better at talking to all kinds of different people. 

Sometimes that comes with being less preachy about the sciences. In the DST example, we realize that people may have other reasons for wanting something different. Everything is not just about the things that we, as chronologists, care about.

And then there are methods of communicating science. Twitter is now becoming a standard tool for communicating science at the technical level, and we are quite active on Twitter. Nowadays, I think Twitter, at least in the chronobiology field, is here to stay. If we want to reach other audiences, we obviously have to go beyond just Twitter, such as videos and visuals on TikTok.

I struggle with using videos and visuals to tell a story about chronobiology. Our research is publicly funded: the taxpayer basically funds our research. This means that we have an obligation to report our findings back to the public and help them understand and lead better lives. Scientists, who are good at writing papers, have to communicate better with the public by creating content for social media, such as this very interview, but generating content takes a lot of time and effort. 

And of course, scientists are busy people who have lots of tasks on their plates. There is a group of people who are convinced that the pluses outweigh the minuses, and that they should generate content. But then there are people who would like to generate content, but they just do not have any bandwidth or they do not really know how to do it. That’s the bottleneck, really.

I think postdocs and PhD students are much more familiar with these tools. Some of them are creative and they already generate content. Actually, during SRBR, we did this trainee session on why public outreach is important on social media and how people can get involved. 

We asked others in the chrono-community, “How has being on social media helped your science?” This question presented an interesting opportunity to network among a community of friends who maintained connections and continued to ask questions during the pandemic.

So it sounds like there are a lot of pros to being online.

One must concede that while social media is great, there are some negatives and some people do not use social media. Just talking to an audience on social media platforms is not sufficient, and one has to look at other ways to reach other groups of people, such as speaking in different spaces. If you are senior, maybe you can get interviewed by a magazine or a newspaper, for example, the New York Times. 

So a recent example is John Hogenesch’s article, which was published in the New York Times about a month ago. It is a whole write-up on health and circadian medicine, arguing the case for why we should do it.

I wanted to take the last few minutes to ask if you had any work of yours that we haven’t touched on yet that you would like to highlight.

One recent controversial (not so in my opinion) practice is the use of Venn diagrams in circadian biology studies because it tends to overestimate the impact of all interventions on the circadian clock. This study was published last year which has had a very broad impact, not just in chronobiology but in all kinds of omics studies. One of my passions is teaching. I host trainee sessions where I teach people about the analysis of circadian rhythms, and have taught at two summer schools and three trainee days. I do this regularly to help people analyze circadian rhythms, and in the end, do the science correctly.