Transitions in development – an interview with Kara McKinley

Let's start at the beginning – when did you first become interested in science?

When I started university, I initially wanted to go into politics. Although I had loved aspects of science in high school, my classes involved a lot of rote memorisations of content. I wanted to make a difference in the world, and I hadn't yet learned that this was possible through a career in research. Following an internship in Washington DC, I realised that politics was probably not for me. Fortunately, I was still taking a lot of science classes to keep my options open. I thought if I was not going to be a politician, I might become a scientist. In contrast to my experience as an intern in politics (which involved a lot of menial tasks), I liked that scientists could be important contributors to the scientific enterprise at any level of their career: undergraduates in research labs can make major discoveries and publish papers! At Princeton University, where I was an undergraduate, every student was required to undertake a thesis project, which gave me the push I needed to join a lab. I joined Michael Hecht's research group, where they were screening libraries of de novo designed proteins to see if any were functional. Working alongside a PhD student in the lab, Mike Fisher, we found that one of these proteins could rescue deletion of an essential gene in E. coli (Fisher et al., 2011). This was when I first felt the joy of a new scientific discovery within a research space, and this experience made me fall in love with science.

How did you come to do a PhD in Iain Cheeseman's lab, and can you summarise the key findings from your PhD project?

Although I came out of my undergraduate degree with a real love of research, my perspective on scientific problems was still quite narrow. I went to pursue a PhD at the Massachusetts Institute of Technology (MIT), fairly certain that I wanted to work on protein folding problems. However, the PhD curriculum at MIT has a session at the start of the year, where all the faculty presents their work to the students. Iain Cheeseman presented on the beauty of cell division. I subsequently decided to join the Cheeseman lab, partly because I thought Iain was awesome, and also because I was fascinated by a specific cell division problem: the immortal strand hypothesis (Cairns, 1975), which proposed that biased chromosome segregation occurred in stem cells. Unfortunately, that project failed within my first 8 months in the lab, but Iain was an excellent, strategic mentor. While I worked on the immortal strand hypothesis, he had also encouraged me to identify a project that was better aligned with the core expertise of the lab. In particular, I was interested in how the centromere is inherited; this project appealed to me because one of the potential ways in which biased chromosome segregation might happen would be if the centromere were bigger on one sister chromatid. Through my PhD work, I found that a kinase, polo-like kinase 1 or Plk1, serves as a regulator for initiating the deposition of a centromere-specific histone in human cells, which is a fundamental requirement for faithful centromere inheritance (McKinley and Cheeseman, 2014). Since then, it has been really fun to see the development of this field to its current state. Recently, two beautiful papers published in Science (Parashara et al., 2024; Conti et al., 2024) reported mechanistic work on Plk1 in centromere inheritance. When these papers were preprinted, one of them pointed out that our paper came out a decade ago, which makes me feel very old.

You moved to Ronald Vale's lab at the University of California San Francisco (UCSF) for your postdoc, but your research projects were very distinct from the focus of that lab. Can you tell us about your career choice, and give us a summary of your postdoctoral research?

Even though my interest in the immortal strand hypothesis ostensibly went nowhere, it reflected an interest in how the cell division machinery might be modified in the context of specialised divisions, like stem cell divisions. For my postdoc, I wanted to investigate how cell division processes were shaped by tissue context. I went to Ron's lab because both he and his research team seemed amazing. Ron is best known for his work on motor proteins and microtubules. When I went to visit the Vale lab, I realised that the group consisted of people working on diverse projects, but unified by their love of microscopy. I wanted to image cells within mammalian tissues, but the challenge was that Ron's lab did not have experience with mouse work. This was when we connected with Ophir Klein, also at UCSF. Ophir's lab does a lot of beautiful work on intestinal stem cell biology using, among other things, intestinal organoids. When I saw that these organoids recapitulated intestinal physiology in a highly tractable manner for live-cell imaging, I knew I had found what I was looking for. Ophir was incredibly generous in welcoming me into his group.

Could you highlight some of the most important considerations you had in mind when looking for group leader positions?

My main suggestion to people developing their application materials is to be true to themselves. We spend a lot of time in science thinking about strategy. It is important to be strategic in some cases in science, like while writing a grant. However, I think it's easy to get caught up in saying what we think is ‘the right thing’ to succeed, so much so that we can lose sight of what we are truly passionate about. A significant deciding factor to succeed in the academic job market is to excite people about our scientific work and aspirations. The best way to do so is by being excited about it ourselves! Don't get me wrong, I also put a lot of strategy into my faculty applications, because I wanted to work on the endometrium without having any previous track record in the field, which made it essential to justify my pivot very carefully. So, I am not saying that there is no space for strategy, but it is important to choose to be unbounded by what one thinks everyone else wants. I often reflect on some great advice that Ron once gave me: ‘What if you just told the truth?’.

You have shared a thorough summary detailing your insights on the market for a tenure-track job. Can you tell us how you chose which position to accept?

In most institutions in the USA, the interview process for becoming an independent group leader includes a chalk talk. This usually involves discussing the plans for one's lab with faculty members in the department without using any slides. I really liked the way the department at Harvard University thought about and supported my science during the chalk talk. I know a lot of people who also went to the institution where they had their best (most fun, stimulating, constructive) chalk talk. While they are an important part of a hiring committee's evaluation of a candidate, they can also give the candidate a strong insight into how the department's faculty interact with their colleagues. At the end of the day, we need to find it stimulating to talk with the people in proximity to us because a lab is not run in a vacuum, and great neighbours make science more interesting. [For further details, see https://www.mckinleylab.org/resources]

What have been the best and, conversely, the most challenging moments as a PI so far?

The best moments have been watching new projects emerge in my lab. It is fascinating to see the new discoveries and directions that come out when my lab members bring their own strengths, preferences and visions. Currently, my lab is not working on any of the projects that were in my original proposal for my job application. My job proposal was the product of my brain alone, whereas my lab is a product of the brains of all the current and past members of my lab, which is so much more interesting.

One of the hardest parts of being a PI is letting go of the perfect vision I had of who I would be as a PI. When training in other labs during doctoral or postdoctoral research, we often imagine a perfect lab for our future selves. However, when the time comes for us to run the lab and make the hard decisions, we get to see pieces of the bigger picture. We now see things that we were not privy to in somebody else's lab. Often, there are scenarios where we must choose between multiple outcomes that will all be sub-optimal for someone. There are also moments when you feel less than you would hope to be, in part because you are a normal, imperfect human being, and in part because you are learning on the fly. This is a very challenging part of the job; it has profoundly reshaped how I look back on my own training and the gratitude I have for my mentors. Mental health support is really important for new PIs, and I wish we were more open about this subject.

Can you summarise the research themes of your group?

Broadly speaking, we study the biology of menstruation and regeneration in the uterus using rodent models. We are interested in menstruation as an example of physiological damage and regeneration in mammals. We have a sense of wonder about a tissue system that destroys and rebuilds itself month after month, which makes the uterus a powerful system for understanding and harnessing regenerative capacity. On the flip side, however, most people who menstruate do not find the experience to be wonderful. That is why we are also extremely interested in quality-of-life impacts of menstruation that have remained systemically ignored.

How do you think we can make the community more aware of the need to increase research output in female reproductive health?

I think it's an exciting time to be in this field because it is coming out of the shadows a bit. One of the challenges for the funding ecosystem (and for us as scientists) is that the health of anyone who is not a cisgender man has been deprioritised or forgotten on a global scale. This must be corrected to ensure that all bodies are represented within the medical ecosystem. So, along with emphasising research on the uterus, we also need to prioritise science that, for example, studies the heart or the brain of women, or studies the musculoskeletal system of someone on gender-affirming care. The biology of the female reproductive system is extremely important, and we also need to study biology of the entire body across a variety of different manifestations of sex. We need to increase funding opportunities and awareness in proportion to how big and broad the knowledge gaps are.

How did you navigate the field to find your niche?

I was inspired by Margherita Turco (Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland), who developed an endometrial organoid protocol to recapitulate endometrial function in vitro (Turco et al., 2017). This work was published when I was early in my postdoc working on intestinal organoids. My initial response was that endometrial biology could be an exciting area for live microscopy. As I became more interested in the field, I broadened my scope to consider the endometrium as an exciting physiological system that could be used to study many different aspects of biology. Over time, I have become more interested in the wide variation in menstrual experiences. In my opinion, there are not compelling definitions of normal and healthy in this space, and so I am invested in understanding variations in menstrual experience and the related biology.

You're organising the Keystone symposium on Regenerative Biology of the Female Reproductive System in 2025. Could you tell our readers more about the meeting and your experience as an organiser?

I am thrilled that Keystone was interested in doing this meeting because we think it's a unique opportunity to bring together people who work on different aspects of the female reproductive system. My co-organisers and I are excited about the opportunity to bring together scientists who have been in the field for a long time, as well as those who are new. As I recently came into the field myself, I know that it's a rich space and we need everyone's best effort to make real progress in people's lives. It's going to be a very fun opportunity for early-career researchers who are either thinking about getting in the field or looking to establish their own labs in the field.

I understand that you are a strong supporter of sharing knowledge about how to succeed in science. Could you tell us more about this philosophy?

Nowadays, there is an increasing appreciation of this concept of the hidden curriculum or hidden knowledge, which is present at all levels of academia. For example, undergraduate students often don't understand the importance of attending office hours or that you can be paid to get a PhD in the sciences. This lack of transparency around the system can deplete the talent pool artificially and unnecessarily. Personally, I am focussed on making the application process for faculty positions more accessible, especially for people of marginalised identities. Several aspects of getting a faculty position require knowledge about what search committees ‘want’, and we often select against people who are not aware of the rules of the game. Much of this hidden knowledge is only learnt after someone is already in the job, which is when it is least useful! Ideally, we want a scenario where everyone is presented at their best during the selection process. The reason many people can't take their best shot is just a lack of access to information about the norms of the process. There are bigger questions to be asked within the ecosystem about how our selection processes work. That said, having co-chaired a faculty search committee, I understand the problem of having to parse a large volume of applications with limited human power. As an individual, I feel that a contribution I can make in this space right now is to formalise information about the likeliest ways to succeed within the existing selection processes. I hope we'll manage to overhaul the evaluation process eventually.

As a postdoc, you founded the Leading Edge Fellows Programme to support women and non-binary postdocs from across the biological sciences. What was the motivation for setting up this programme?

The motivation comes from the observation that, despite incredible gender diverse talent at the postdoc level, a significant majority of faculty applications in most institutions still come from men. The goal of the Leading Edge Fellows Programme is to shine a spotlight on all the brilliant women and gender marginalised postdoctoral researchers, who are already in the academic pipeline. We intend to create environments to help these populations feel equipped to apply for faculty positions in the biological sciences. The community of Leading Edge has been especially important in equalising access to information. At the heart of this is a strong sense of community and trust, where Fellows feel able to share unpolished work and tough experiences, knowing that they will receive feedback, advice, empathy and support. There is a very strong ‘abundance mindset’ within Leading Edge – the idea that there is enough space for everyone to thrive.

In addition, a major strength of Leading Edge is that it is cross-institutional. Leading Edge Fellows are at 84 academic institutions around the world. This platform also provides an opportunity to cross-pollinate information across people who have access to very different resources and experiences, and receive very different advice. The Leading Edge Fellows find the information they learn from one another so valuable that they aim to share it as broadly as possible. So far, the Leading Edge Fellows have written five peer-reviewed papers on aspects of a career in academia (McKinley et al., 2022; Kong et al., 2023; Martin et al., 2023; Bayin et al., 2023; Vlasits et al., 2023) and a few informal pieces.

How do you find the time to keep running this programme alongside your commitments as an independent PI?

As Leading Edge has grown, the fellows from earlier cohorts have taken on a lot of the responsibility. The workload was enormous in the beginning. But as we progressed, one of the most important metrics of success for the programme is that people choose to stay in the community and continue to invest in it. We don't currently have a policy about when you stop being a Leading Edge Fellow. Everyone just stays! So a lot of the programming is now coordinated by Fellows from earlier cohorts. I have been very lucky that so many people have been invested in sustaining the programme and pushing it forward.

Did you ever consider an alternative/non-academic career path? What and why?

During my postdoc, I tried to interrogate why I thought I wanted to be a PI. I tried to distill what I wanted out of my career into things that I value, which are agnostic to any profession. In my case, I love working with people who are smarter than me and I want to do good in the world. So one of the careers that jumped out to me was in the grant making space, which is a really cool profession; I wish we talked about it more as potential path to take after a PhD. I toyed with the idea of a position of a programme officer, for example within a private foundation. A big turning point for me in deciding to be a PI was finding a problem that I found so important that I really wanted to invest my whole career in working on it.

Finally, is there anything Development readers would be surprised to learn about you?

I don't know if people would be surprised to know this about me, but I am a terrible cook. People always say that cooking is like doing an experiment, and you must be a good cook if you are a good scientist. But I am here to tell you that is not true!

Kara McKinley was interviewed by Saanjbati Adhikari, Features Editor at The Company of Biologists. This piece has been edited and condensed with approval from the interviewee.