Prof. Dr. Julie Claycomb

Written by Paula Petronela Groza

Dr. Julie Claycomb, a “farmgirl” from the rural part of Pennsylvania who dared to pursue the academic path, was recently promoted to the rank of Professor within the Department of Molecular Genetics at the University of Toronto. Because she was interested in law and politics as well as biology, Dr. Claycomb pursued a double B.A./B.S. degree in Political Science and Biology at University of Pittsburgh, Pennsylvania. While she was an undergraduate, she had the opportunity to explore bacteriophages with Dr. Graham Hatfull as an HHMI undergraduate fellow, which solidified her goal of a career in biology research and teaching. After graduation she pursued her love of biology by starting her PhD under the supervision of Dr. Terry Orr-Weaver at Whitehead Institute/Massachusetts Institute of Technology, Cambridge, MA, USA. At that time, her research focused on germline gene regulation and how Drosophila follicle cells in the ovary amplify or over replicate clusters of eggshell genes to rapidly pump out many eggshell proteins.

Following her doctoral training, Dr. Claycomb wanted to challenge herself by changing  model systems (from flies to worms) and research topics for her postdoc, so she joined the lab of Nobel Prize Laureate Dr. Craig Mello at UMass Medical School. Working with Dr. Mello at the time he was co-awarded the Nobel Prize with Dr. Andrew Fire for understanding the mechanisms of RNA interference served to energize and inspire Dr. Claycomb, particularly because it was pure curiosity and the pursuit of fundamental questions through clever and careful experiments that led Drs. Fire and Mello to these discoveries. In the Mello lab, her scientific path took an unexpected turn as she was given the opportunity to explore a different project than she initially envisioned. The project aimed to study an Argonaute (AGO) protein, the loss of which caused fertility and chromosome segregation defects. That unexpected project was the catalyst that gave rise to the research questions she is currently addressing as a principal investigator. Many of her lab’s key questions gravitate around the concept of cooperation and competition between RNA interference pathways in the regulation of germline genes in the context of a hermaphrodite organism capable of producing both sperm and oocytes in the same gonad.

Recently, her team completed the comprehensive characterization of all 19 C. elegans AGO proteins, with many of them being characterized for the first time. Her team’s tour de force manuscript which includes data on small RNA binding partners, localization patterns, and mutant phenotypes of the 19 AGO proteins can be read here. The hope and expectation that this work will help the field evolve faster is already being fulfilled as it has already helped others understand processes that they’ve been studying, publish papers and open new lines of investigation for their labs (for example, the lab of Dr. Alla Grishok made some surprising new links between miRNA pathway AGOs and a conserved histone methyl transferase using these new data)! Her team also continues to build on these findings, as well, with the lab’s current areas of focus being: (1) to explore the possibility that AGOs could be mobilized from the intestine to other tissues, (2) to understand how AGOs interact with small RNAs from the environment, (3) to decipher the tissue specific actions of AGOs, and (4) to learn how structural differences modulate AGO function(s). For the first topic, they get both inspiration and help from Dr. Amy Buck, a friend and collaborator, at Edinburgh University. Specifically, Dr. Buck’s lab has shown that an AGO from a parasitic nematode is secreted via extracellular vesicles and taken up by host cells in the intestines of mice. The lab’s second exciting research arc examines the phenomenon of transgenerational epigenetic inheritance in C. elegans.  Specifically, her team is testing the possibility that small RNAs serve as a type of heritable “molecular memory” of stresses and experiences in ancestors. She reiterates that worms are outstanding models for understanding this phenomenon, given their well-known genetics, robust responses, and well-developed tools for studying these pathways. We all should stay tuned, as they are working very hard on these research questions and cool findings will be soon revealed!

My overall teaching and mentoring philosophy hinges on conveying enthusiasm for fundamental questions; leading students to develop active questioning approaches and encouraging a genuine curiosity for discovery (…) and to instill in my trainees or students a commitment to sharing their new knowledge with others (“learn one, do one, teach one”).”

Like many PIs, managing all these challenging projects can be overwhelming at times, but she has a secret weapon that always grounds and re-focuses her and her lab when things become a bit intense.  It’s simply a tiny piece of note paper in her office with a treasured message written by her dear friend and mentor during the grad school, Dr. Gio Bosco, which reminds her to “keep them small and do them well!”. She returns to that advice when deciding how to approach research projects and questions. Most often, she breaks the big questions down into manageable pieces and tackles them one by one, always focusing on the experiments most likely to yield high quality data. Her advice for others is “Instead of trying to do it all, prioritize your experiments and ask the key questions.”

Over the years, Dr. Claycomb has successfully developed and used skills that she learned both inside and outside academia to help her navigate the academic life. As a group leader, she says that her business-shaped way of thinking was acquired from her experiences from when she was helping her family run their business, a small ice cream and hamburger stand in rural Pennsylvania. Simply, she sees running a lab like running a small business. Therefore, each successful step that one of her trainees takes, from getting beautiful qPCR data all the way up to obtaining their dream job, are all rewarding achievements to her. As a teacher, she believes that the most valuable aspect in teaching is to be able to transmit enthusiasm to the students. She achieves this by reminding herself how she felt when learning that subject and by having empathy for her students as individuals.

As a woman in science, she has experienced microaggressions and sometimes even more blatant harassment. Such moments always come as a shock to her. Even though she doesn’t always handle them as well as she would like in the moment, she is constantly trying to learn better strategies to speak up for herself and to support or advocate for others, especially mentees who also experience harassment. One way of coping is through connecting people and building communities where people feel safe to share not only their coolest new data but also their struggles. For instance, with several other researchers, she contributed on putting together a series of monthly Worm Small RNA Seminars on Zoom which has become a vibrant place for the field to discuss data and ideas. As a Board Member for the RNA Society (2023-2024) she aims to unite the RNA community and implement practical solutions to improve the inclusion and experiences of parents at RNA Society conferences. Her goals include having the RNA Society provide more childcare grants, caregiver and child travel grants, and potentially (ideally) on-site conference childcare. As a parent herself, she finds these initiatives incredibly important for supporting both faculty and trainees, particularly women with children. Recently, she has also become deeply involved in expanding and uniting RNA researchers across Canada through the group RNA Canada ARN.

Her years of experience have taught her that, as a principal investigator, it is important to center one’s day around writing, reading, and thinking, because those activities are the key to building the base for great ideas. Yet, it’s just as important to focus on things that bring you joy and keep your priorities and values in focus. Her advice for trainees is to always be experimentally fearless, perseverant, and creative in getting answers to the important questions they are pursuing. Also, one should not worry about the outcome of an experiment, but just try doing it (“Just do it!”) and keep doing it – this being her guiding strategy while in grad school.

Being surrounded by well-intentioned people who share similar interests is a great asset. Thus, she sees being part of the RNA Society COMMUNITY is its greatest benefit for its members. The world-wide community that the RNA Society has established gives her many things. These include a feeling of belonging, the ability to contribute to a global RNA community, a means of connecting with new friends and collaborators, the possibility to learn about the hottest topics through both the yearly meeting and the RNA Journal, and plus other career-focused initiatives. A cherished memory in the heart of the RNA Society community is her participation at the RNA Society meeting in Kyoto (2016). She recalls a mix of great food, exciting science, small RNA satellite workshop organized by Dr. Yuki Tomari in Tokyo, and breathtaking sites in both cities made this particular meeting a once in a lifetime experience. In addition, there were some personal moments that filled her heart with joy such as her PhD student Monica Wu won a poster prize, finding out that she had received tenure, and being lucky to share it with her husband, Dr. Alex Ensminger, who was also a meeting attendee.

She is very fond of small RNAs in general, and her favorites are C. elegans 22G-RNAs, although she admits that piRNAs are ‘pretty cool’ too. Mechanistic studies providing insights into how molecular machines in small RNA pathways function are among her favorite articles to read. A recent one she remembers reading with enjoyment is by the lab of her friend, Dr. Yuki Tomari, “The two Gtsf paralogs in silkworms orthogonally activate their partner PIWI proteins for target cleavage.”  

If you are interested in learning more about the Claycomb lab, go to lab’s website.  To get in contact with Dr. Claycomb, you can find her at @farmgirlPhD and @ClaycombLabUT.