PEOPLE & IDEAS Dan Davis: Up close and personal with immune cells Nicole Infarinato

Davis uses microscopy and imaging approaches to study immune cell interactions.

Dan Davis was initially drawn to research by was. In 1995, I wrote to many different his ambition to pursue some of the biggest laboratory heads in the United States, in- questions in science—those that deal with cluding Ahmed Zewail (the Nobel laureate the fundamental laws of the universe. He who studied femtosecond chemistry) and began his scientific career as a physicist, but Franz-Ulrich Hartl (who studies protein Davis’ curiosity eventually shifted from the folding). I was thrilled that so many emi- Downloaded from http://rupress.org/jcb/article-pdf/217/9/2975/1380226/jcb_201808060.pdf by guest on 30 September 2021 laws that govern the universe to the details nent scientists replied to me, and I still have of how life works. It was these evolving pas- a file with all their letters and faxes. I ended sions that compelled him to become both a up heading to Harvard University to work biologist and a writer. Davis was raised in with immunologist Jack Strominger. London, and although his parents remem- ber his early aspirations of becoming a “What makes microscopy fun is that it farmer, he tells us that he always wanted to is so inherently explorative.” be a scientist. After earning his PhD in phys- ics, Davis delved headfirst into the world of I remember arriving in Boston in the immunology as a postdoc at Harvard Uni- midst of a snow blizzard and staying in a versity in the laboratory of Dr. Jack Strom- youth hostel. The next day in the labora- inger. Before he was thirty years old, Davis tory I was completely overwhelmed seeing Dan Davis. PHOTO COURTESY OF NEVILLE MILES. had established a laboratory of his own in racks of plastic tubes, countless bottles, the UK. Today, Davis and his team take a and pipettes—the things that were worlds What first drew you to study NK cells? zoomed-in approach to immunology, har- apart from anything I was used to working I arrived in Jack Strominger’s laboratory nessing his unique perspective as a physicist with in physics. I immersed myself in it all, at Harvard University at a time when our to implement sophisticated high-resolution reading textbooks and papers and working understanding of molecular recognition by imaging techniques and spy on the behav- long hours made fun by the friendship and human NK cells was opening up. These cells ior of immune cells. In addition to his work camaraderie of other postdocs. Within six were identified in 1975 as immune cells po- in the laboratory, Davis is an accomplished months, working with postdocs Ofer Man- tent at attacking cancer cells. I realized that author of two immunology-based books for delboim and Hugh Reyburn, we found that while the important receptors and ligands the public, which are examples of his many T cells express cell surface receptors previ- were being identified (and from crystal efforts to bridge the gap between academia ously associated with Natural Killer (NK) structures and site-directed mutagenesis, and the rest of the world. cells (1). This was an early example of an their interaction could be pinned down We reached out to Davis to learn more interesting theme in immune cell biology: with atomic resolution) there was still a gap about his scientific trajectory and current protein expression once thought to be spe- in understanding what actually happened research pursuits. cific for one type of immune cell also turns over the few minutes that NK cells took to out to be important for other immune cells. make a decision about the state of health Where and with whom have you studied? We now know that it is hard to define the of other cells. I wanted to visualize human I did my undergraduate degree in physics differences between types of immune cells immune cell interactions, to directly watch at the University of Manchester. I chose because the variability is enormous. Single what happens over the few minutes that an Manchester for the buzz of the music scene cell sequencing and other technologies have NK cell discerns the state of health of an- at the time. I obtained a PhD in physics shown that, at some level, every cell has its other cell it is in contact with. So I tagged at Strathclyde University, Glasgow, Scot- own uniqueness. It was at this time early one of the vital proteins in this interaction, land, working with Professor David Birch. in my postdoc position that I began to gain class I MHC protein, with GFP and watched After my PhD, I wanted to switch to study some confidence in my ability to contribute, cells interact. From this, I discovered the some aspect of human biology because it while also realizing how much of one’s life NK cell immune synapse (2), an unex- seemed to me that was where the action has to be dedicated to science to do so. pected dynamic molecular choreography at ninfarinat@rockefeller​ .edu​ . © 2018 Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://​www​.rupress​.org/​terms/​). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://​creativecommons​.org/​licenses/​by​-nc​-sa/​4​.0/​).

Rockefeller University Press https://doi.org/10.1083/jcb.201808060 2975 J. Cell Biol. 2018 Vol. 217 No. 9 2975–2976 What kind of approach do you bring to What do you enjoy doing outside of the your work? laboratory? What makes microscopy fun is that it is so in- I have written two popular-level books and herently explorative. Some lines of research presented them on TV, on the radio, and at in my laboratory address specific mechanis- many science and literary festivals. Writing tic problems, such as how cytoskeletal dy- doesn’t quite feel like a hobby though, as namics allow secretion of lytic granules out it’s a big part of my life. My first book, The of an immune cell to kill a cancer cell. But Compatibility Gene, told the story of the many of our discoveries have come from see- human leukocyte antigen system and how ing something unexpected down the micro- these few genes impact our health and indi- scope and following it up. Just by watching viduality (6). One of the great joys in writing cells move around, for example, we discov- that book was interviewing many of the in- ered long thin strands of membrane that we spiring scientists who were involved in the called membrane nanotubes, which can keep discoveries, some of whom are no longer A super-resolution microscopy image of filamentous immune cells and other cells connected over with us. My most recent book, The Beautiful Downloaded from http://rupress.org/jcb/article-pdf/217/9/2975/1380226/jcb_201808060.pdf by guest on 30 September 2021 actin in a migrating human NK cell. IMAGE COURTESY OF long distances. We then found that mem- Cure, more broadly describes the scientific ASHLEY AMBROSE AND DANIEL M. DAVIS. brane nanotubes can provide a route for HIV quest to understand the immune system the contact immune cells make with other to spread from one T cell to another (4). More and how this knowledge unlocks new ideas cells, reminiscent of what had very recently recently, although we never set out to specif- for medicine (7). I know this might come been discovered for T cells by Avi Kupfer, ically understand how immune cells detach across as boasting, but one of my own favor- Mike Dustin, and their colleagues. At 28, I from a target cell after immune surveillance, ite writers, Bill Bryson, said he enjoyed both left Harvard to set up my own laboratory at by watching this happen and digging into of my books. Whenever I remember that, it Imperial College London focused on imag- the details, we stumbled across a process for always makes me smile. ing immune cell biology. In between jobs, this that involves shedding the activating my girlfriend and I traveled around Mex- receptors from the immune synapse. This is Any tips for a successful research career? ico, where faxes chased me across hotels important for how immune cells sequentially I like Kurt Vonnegut’s advice best of all: and youth hostels, each a new iteration of move from one target cell to another so that “There’s only one rule that I know of, our response to reviewers for our paper de- one immune cell can serially kill several dis- babies—God damn it, you’ve got to be kind.” scribing the immune synapse. eased cells where appropriate (5). 1. Mandelboim, O., et al. 1996. Science. 274:2097–2100. 2. Davis, D.M., et al. 1999. Proc. Natl. Acad. Sci. USA. What are you currently working on and What has been the biggest challenge in 96:15062–15067. what is up next for you? your career so far? 3. Lopes, F.B., et al. 2017. J. Cell Biol. 216:1123–1141. Building on my background in physics, my A great challenge for me has been to not take 4. Sowinski, S., et al. 2008. Nat. Cell Biol. 10:211–219. laboratory has always strived to use novel on too many things, but to focus on trying to 5. Srpan, K., et al. 2018. J. Cell Biol. https://doi​ .org/​ 10​ .1083/​ ​ jcb.201712085​ fluorescence microscopy techniques to vi- do a few things well. As an academic, there 6. Davis, D.M. 2013. The Compatibility Gene. Allen Lane, sualize key molecular components of the are so many things one could be doing: re- London. immune response with ever-increasing search, teaching, reviewing, supervising, 7. Davis, D.M. 2018. The Beautiful Cure. Bodley Head, London. precision. For some years now, we have committee work, public talks, school talks, been using super-resolution microscopes attending conferences, organizing confer- to study the integration of signals from im- ences, and so on. I find it hard to say no, but I mune cell surface receptors. An emergent think sometimes you just have to. theme across the work of many laborato- ries is that the classic Singer-Nicholson What is the best advice you have been fluid mosaic model of unstructured cell given? membrane organization is too simplistic One piece of advice that often plays in my because many cell surface proteins are or- mind is something a physician once said to ganized on a nanoscale. We have recently me: You have to set out boundaries between shown, for example, that clusters of in- you and your work because otherwise things hibitory (SIRPα) and activating (FcγRI) will get out of hand and feel overwhelming. receptors coalesce at the surface of human You have to be careful, for example, to not macrophages but segregate upon Fc recep- let feelings that come from experiments not tor activation of macrophages (3). This working in the laboratory spill over into other raises new questions about how and why parts of your life. And imagine if you discov- different receptors are organized into na- ered something really big, say a new cure for noscale clusters at cell surfaces and how HIV. Everyone would want a piece of you for all the proximity of different receptors im- different reasons and the only way to survive More than a hobby: The Beautiful Cure. PHOTO COUR- pacts signal integration. and stay sane would be to have boundaries. TESY OF JULIA CONNOLLY, PENGUIN RANDOM HOUSE.

Infarinato Journal of Cell Biology 2976 Dan Davis: Up close and personal with immune cells https://doi.org/10.1083/jcb.201808060