Meet a Whitehead Postdoc: Henry Kilgore

Henry Kilgore is a postdoc in Whitehead Institute Member Richard Young’s lab working on understanding how protein chemistry influences where in the cell proteins localize. We sat down with Henry to learn more about him and his experiences in and out of the lab.

What is the current focus of your research?

Recently I’ve been working on understanding a new type of code that we found in protein sequences that guides a protein to its destination within cells, and understanding more generally what it is about molecules that causes them to arrive at different subcellular destinations.

Rick [Young] and I collaborated with computer scientists to develop a machine learning algorithm that can predict a protein’s destination, or localization, based on its amino acid code. Researchers already knew that a protein’s amino acid code contains information on its three-dimensional structure, and had made algorithms that predict this structure. Now we show that proteins contain this other code for localization, which is in my mind wholly complementary to protein structure in terms of determining function. The structure helps the protein to do chemical reactions, interact with partners and perform any number of other functions. However, if the protein ends up in the wrong place in the cell, it has very limited ability to perform those functions because none of the molecules it needs to interact with will be present there. Our work shows that this is likely a common disease mechanism: mutations to the localization code cause a protein to go to the wrong spot, so it cannot perform its function—which means that understanding the code could lead to new strategies for treating diseases, including diseases that do not currently have good treatment options.

When you were a kid, what did you want to be when you grew up?

I wanted to be a veterinarian. I love animals. I've had dogs, guinea pigs, cats, and various reptiles over the years. I wanted to work with animals for a long time as a kid. I think it didn't work out because I liked them so much that I couldn't imagine myself having to perform medical operations on them.

How did you become interested in a career in science?

I became interested in my early teens. I would read or see documentaries about scientists who were working at the advent of quantum mechanics and these profound discoveries that they had made, and I thought that was really inspiring: that there's stuff out there in the universe that is so different from our everyday experience that it caused people to grapple in a very serious way with philosophy and their own perspectives on the natural world. Also, I was raised spending a lot of time outdoors. We would always go on family trips into the mountains in California. The place I grew up in is rural and surrounded by chaparral, which is a type of ecosystem that is essentially dunes with oak trees and stuff on them. I would go out with my dog, or with my friends and our dogs, and go hiking or ride dirt bikes through the area. I was really immersed in nature and then exposed to new ways of thinking about nature, and the two blended to produce my scientific interest.

It sounds like you had very interdisciplinary interests. How did you end up in your current field?

I started my scientific career as a professional bird watcher. Early in undergrad, I worked at the Coal Oil Point Natural Reserve in Santa Barbara, recording the comings and goings of snowy plovers on the beaches. Snowy plovers evolved to put their nests in the dunes, just on the ground, and people like to walk through the dunes, which disturbs the nests. There was a grassroots effort by scientists at UCSB and local people to protect this bird that was really important to that ecosystem. Being part of that led me to develop an interest in biology and ecology, but I also really wanted to understand how the universe worked at a very detailed level. That’s what attracted me to chemistry, which is sometimes called the central science because it provides you with the background knowledge to understand much of the physics that's going on with molecules, and to think about how things can interact in a very detailed way at the levels of quantum mechanics or electrostatics, for example. I worked in this hybrid space of chemistry and biology as a PhD student, and I would say that background serves me really well in my current work.

What are your hobbies? 

As I said, growing up I spent a lot of time hiking in the mountains of California, and from that, I started getting into backpacking. I think I've backpacked thousands of miles at this point, in North America, Africa, and Europe. It’s a fantastic way to experience nature and to unplug from the cell phones and screens that folks are always staring at. Recently, I've gotten more into mountaineering, which is a great way to get through the winters here in Boston and spend more time outside. What I've been doing for the last couple of winters is mountaineering in the White Mountains or the Rockies and engaging and interacting with nature in a way that a lot of people may not have, but I suggest they should. There's a lot of beauty in the wintertime that we don't always see.

How do you balance your love of being outdoors with a job that requires a lot of time spent in front of a computer?

Scientists are always looking for sources of inspiration and ways of being creative, trying to develop a creative process that allows us to think about our research problems. I see my interest in the outdoors as being a catalyst for my scientific activities and capabilities, because when I'm outside and doing physical exercise, my brain is playing games with the problems I’m working on. I've come up with any number of research ideas on a hike, just chatting with someone and talking through problems or just reflecting internally. I just feel freer to engage other ideas in that setting: it’s easier to think about the world in a way that’s less tied down. Then, afterwards, I need to go sit inside to really hammer things out, so the two ways of being complement each other.

Do you have other hobbies?

I play a good bit of guitar; I've been a musician since I was about 13 years old. I like to train for a marathon or two each year. I’m also a first-class beach bum and an armchair historian, so I read a lot of history books and listen to podcasts in my spare time, ideally on a beach. The two really synergize well. I'm a science junkie as well, so I read about all sorts of research too. Few things have proven as exciting to me as discovering a new scientific discipline and diving into it.

Do you collect anything?

Fossils, kind of. I love paleontology, especially as it pertains to dinosaurs and the post-Cretaceous Period animals. Near the little town where I grew up in Southern California, there's actually a big hillside that just sheds fossils continuously. They're the ones that all the local museums say: we've got 500 of these, enjoy! So, folks will take them home. I’ve got a handful of those fossils at my house, and if I’m in a place where I know there are fossils, I might see if I can find anything of interest. I also have an enormous closet full of outdoors equipment, which is looking forward to taking over a garage someday.

What’s a fun fact a friend might share about you?

They might ask me to tell you about my favorite ice cream place in Massachusetts. As readers may know, Massachusetts is jam packed with killer ice creameries, but my favorite is Somerset Creamery. It is this fantastic ice cream place located near Old Silver Beach, where we sometimes go for Whitehead Institute retreats. It has a singular Cranberry Bog ice cream, which actually has the taste of cranberries but not so much that it’s overwhelming, and there's crunchiness from walnuts and chocolate chunks, so it’s kind of like you are actually eating a cranberry bog. They also make their waffle cones fresh, with a dash of cinnamon or something magical. The cone is still hot by the time your ice cream hits it, and I don't ever want to eat a waffle cone that’s not hot again.

Where do you see yourself in ten years?

I hope to help realize the promise of using molecule localization to improve the treatment of disease. I think that working as a professor would give me the opportunity to do this. It would also give me the opportunity to mentor and educate people in science, including on how to integrate AI and machine learning into their own research programs. I think that the advancements that we're making today are on the same order of magnitude as anything that's come out of human history, and a decade from now, science might look completely different than it does today. We’re really on the cusp of something fantastic, and it's a super exciting time to be a scientist.

What do you see as the future of AI in research?

I think it's going to enable us to make discoveries that are really transformative to the human experience in a way that we've never been able to do before, or to make them much more quickly than we ever could before. I think overall AI is going to be complementary to human researchers. We're already integrating it into our scientific process, and it’s going to allow us to spend more time thinking creatively and less time doing the repetitive tasks that take up so much of our time currently. 

One area I'm thinking about is drug discovery. Historically, it could take decades to get from the point of a biological discovery, to someone realizing it could have therapeutic applications, trial and error to find a working molecule, iterations of development and refinement, clinical trials, and finally delivering a therapy at scale to patients. I think a realistic reflection of what AI can provide is moving from biological discoveries to treatments on a much quicker timeframe and much more cheaply. In some biotech companies, that’s already taking place. Also, I think that the discoveries we've made in this lab on combining protein language models with other more specific knowledge will absolutely be useful for drug discovery, and that’s very exciting.