Meet the PI
Jeff Farrell, PhD
Earl Stadtman Investigator
Lab Head, Unit on Cell Specification and Differentiation
National Institute of Child Health and Human Development
What is the research focus of your lab? We’re interested in the genetic control of cell specification and differentiation in zebrafish. What cascade of gene expression directs morphological changes in different cell types and how are those programs reused across development? Also, how is cell specification affected by cellular history, such as prior damage or previously expressed transcriptional programs? Combining new technologies (scRNAseq approaches we developed) with timeless approaches (genetics, imaging, embryology) will let us look at these questions from a new angle.
Getting to know you better
Where were you born/where did you grow up? I grew up in Baton Rouge, Louisiana. People are usually surprised by this (until I cook for them) since I don’t have a characteristic accent.
Tell us something about yourself in one sentence. I always have the most fun in science when it’s a good collaboration with someone who thinks differently from me.
Science
Which of the current projects in your lab you are most excited about? I love all my children equally! One project I’m really excited about right now is a single-cell RNAseq timecourse of wild-type zebrafish development; it’s an extension of the work that I did in my post-doc, taking what we did in 2018 farther in development. But I think the data and analysis will be really useful to the rest of the zebrafish community, and we’re working really hard to make it as easily accessible as possible. Another project I’m really excited about is looking at cells that change specification from one cell type to another during the refinement of a boundary between progenitor compartments. How does that affect the cell long-term, and are there mechanisms that specifically enable the transition? I think I’m having fun with that one right now because it’s in the early “dreamy” stage where we have big ideas and the reagents and fish lines we’re trying to build are coming along well, which is always motivating. Like all projects in science, obviously something will happen soon that will require a lot of rethinking or troubleshooting!
What advice would you give to someone considering a career in science/research? In addition to finding scientific questions that motivate you, I think it’s important to spend time figuring out the kinds of work that you do and don’t like – what gives you the biggest thrill and will keep you heading into the lab? Do you like being the first person in the world to see something amazing under the microscope? Do you like the rapid iteration that’s possible with computational analyses? Do you like the absolute precision afforded by biochemistry? Or is it that crazy embryonic phenotype that’s going to get you fired up? Once you know that, I’ll bet that there are lots of cool scientific questions that interest you, but you can make sure to choose work that you will find enjoyable and rewarding. Also, during each career stage, there’s a slump mid-way through when it starts to feel really hard. Don’t give up!
Which part of the PI job you enjoy the most? Why? Well, I’m just getting started, so I’ll bet this answer changes a lot over the next few years. So far, my favorite part has been when my trainees give great lab meeting presentations — to hear their interesting ideas, see their pride over their own work, see their growth, and get a good discussion going.
Outside of work
What do you enjoy doing outside of work/lab? In my (increasingly rare these days) spare time, I’m a potter and make functional ceramics. Many of my friends and family eat or drink from dishes that I’ve made for them. I wish this pandemic would end so that I could find a studio to work in (safely) here in DC.
What career would you have liked if you were not a scientist? That’s a tough one. While I have many passions, most of them make for difficult careers. I probably would have been satisfied becoming a computer programmer, though it would have been important to me to work on the right project.
Present situation
How has the COVID-19 pandemic affected your lab and work? Ha! It has affected all aspects. I opened the lab in January 2020, and then essentially shut it back down March through June. It’s made it much more difficult to train the new members of my lab (from across the room!), and because of staffing restrictions (we only have two people in the lab at a time), it’s made it more difficult to foster the sense of community I want in the lab. Still, we are getting where I want to go — maybe just a little more slowly than I expected. And, it is at least inspiring to see all of the amazing work being done to respond to the pandemic within the NIH and across our global community; this is one of those moments in history that makes you proud(er) to be a scientist.
Caroline Hill, PhD
Senior Group Leader
Francis Crick Institute
What is the research focus of your lab? The fundamental biological problem my lab focuses on is how cells use signal transduction pathways to communicate with each other in the context of whole organisms to regulate new programmes of gene expression and induce new behaviours in their neighbours. This is important, as cell communication underpins normal embryonic development and its deregulation results in numerous human pathologies.
We focus on the signalling pathways induced by the TGF-β family ligands, a group of highly evolutionarily-conserved growth and differentiation factors that signal through serine/threonine kinase receptors and the SMAD transcription factors. These pathways play essential roles in specifying and patterning the germ layers during early vertebrate development, and this is the aspect for which we use zebrafish embryos. Aberrant TGF-β family signalling leads to serious diseases, such as cancer and the Marfan syndromes, among many others. My lab focuses on both physiological and pathological signalling and takes an interdisciplinary approach, combining cell and developmental biology with biochemistry and computational modelling.
How long have you been working with zebrafish? How long have you had your own lab? I have been working on zebrafish since 2008, but have had my own lab since 1995, which was when I started working on TGF-β family signalling. We initially used Xenopus embryos as our developmental model to understand how the TGF-β family ligands Nodal and BMPs are involved in the early specification and patterning events of the vertebrate embryo. As our work progressed, we wanted a more genetically tractable organism that was also amenable to transgenesis and, most importantly, to imaging. I am fascinated by the spatial and temporal regulation of signalling and wanted to be able to visualise it, as the embryos developed. For this, zebrafish embryos obviously have enormous advantages over Xenopus embryos.
Getting to know you better
Where were you born/where did you grow up? I was born and raised in London, UK. I love London as a city and have actually spent the majority of my life living there. I was the first generation of my family to go to university and the first one to pursue a science career. I looked to my teachers at school and university for role models and inspiration, and that experience makes me take very seriously my own responsibility to be a role model for younger scientists.
Tell us something about yourself in one sentence. I was inspired to become a scientist at the age of 11 when I read a biography of Marie Curie.
Science
Which of the current projects in your lab you are most excited about? We want to understand how Nodal signalling, in cooperation with other signalling pathways, determines the specification of mesoderm versus endoderm in vertebrates. This is a super interesting problem as cells literally next to each other at the zebrafish embryo margin during gastrulation, experiencing the same environment, can be specified to different lineages. As genome editing and imaging has become more advanced, we are now developing live imaging technologies that will allow us to be able to directly visualise the signalling status of cells as they are specified to become mesoderm or endoderm progenitors. This will be very exciting if we are successful.
What advice would you give to someone considering a career in science/research? First, I think it is crucial to work on a biological problem that you think is important and that genuinely interests you. From there you need to be prepared to go where the experiments lead you – use whatever systems, organisms, technologies are required to help you answer your question. For a career in science you have to be ready for the long game, and prepared for a lot of set backs along the way. However, at its best it is like being an explorer and nothing beats the feeling of discovering something that no-one else on earth knows!
Which part of the PI job you enjoy the most? Why? There are two aspects of the job that I really enjoy. One is the experience of watching the scientific development of students and postdocs in my lab. They join the lab with a certain level of experience, obviously more for postdocs, and as they take ownership of their project and make discoveries, you see them blossom into excellent scientists, ready for the next stage of their career. The other is discussing the experiments themselves with my lab members and trouble shooting. I loved doing bench work myself and do miss it, so I very much like the process of working out how to solve experimental problems and then having the satisfaction of getting techniques to work and yielding exciting results.
Outside of work
What do you enjoy doing outside of work/lab? I like gardening, and hiking - basically being outdoors around nature. I also like films (I’m married to a film critic), and music (I play the piano and violin).
What career would you have liked if you were not a scientist? A violin maker. When I was a teenager I bought a violin from someone who restored them and who also made them. I was totally blown away by his workshop. The idea of being able to make such a beautiful musical instrument really appealed to me. I still haven’t ruled out giving it a go when I eventually retire!
Present situation
How has the COVID-19 pandemic affected your lab and work? We have actually been quite fortunate. Everyone in the lab coped brilliantly with the 3-month lockdown we experienced in London from March to June. We had lots of data to analyse, and papers and theses to write. Our fish were also very well cared for by our aquarium staff who had key worker status. The lockdown did make me realise that I didn’t much enjoy working from home. In recent years I have made a concerted effort to separate my home and work lives, which has worked very well for me. Dealing with home schooling a teenager at the same time as trying to get on with all my lab and Institute commitments was extremely stressful. On a more positive note, during the lockdown, our Institute (the Francis Crick Institute) developed a COVID testing platform to test local hospital healthcare workers, care home workers and residents and now also all the Crick staff. This has meant that from June, we were able to get back to the lab and work fairly normally as we are tested once a week, and have also put in place a lot of safety measures.