Cell scientist to watch – Ines Drinnenberg

Ines Drinnenberg

What inspired you to become a scientist?

I would say science is something I ‘fell into’ rather than actively pursued; when I was a child, I did have a natural interest in science, but I didn't go out into the garden and collect insects, or anything like that. But when I think about some of the movies I watched, like James Bond, most people were excited by the character James Bond, but I always liked the nerdy scientist characters, so maybe that's where I saw myself. Then, at university, it was the hands-on experience in research projects and getting results in the lab that I realised I was getting very excited about, and I haven't looked back since.

How did you then become interested in the field of evolutionary chromatin biology, now coined ‘EvoChromo’?

This begins with the postdoc I did at the Fred Hutchinson Cancer Research Center in Seattle, jointly between Steve Henikoff's and Harmit Malik's labs. And particularly in the Malik lab, they work on diverse aspects of chromatin evolution. Just by being in the lab, I was able to learn lots about the diversity of chromatin components and the evolutionary mechanisms, beyond the usual suspects that we think of, such as the core histones, H2A, H2B, H3 and H4. That was when I realized chromatin can actually be quite diverse in different eukaryotes. Later, I got in contact with Frédéric Berger, who works at the Gregor Mendel Institute (GMI) in Vienna and also works on different aspects related to chromatin evolution. He thought it would be really exciting to put together some workshops on chromatin evolution and so he involved me in organizing that. Then we had the first workshop, organised by The Company of Biologists, in 2018, which was a huge success; there were talks on really diverse aspects of chromatin, from DNA methylation and imprinting to histone variants and centromere evolution. This has since led to a series of ongoing workshops on chromatin evolution/EvoChromo, which is really exciting.

As well as the postdoc you mentioned at the Fred Hutchinson Cancer Center, you also did your PhD in the US at the Whitehead Institute. Why did you choose to conduct your research in the USA, and was it a big adjustment moving from Europe?

I wouldn't say it was a big adjustment because at that point I was just super excited to move; I wanted to explore, get out of Germany and try something different. Also, I got this great opportunity to work with David Bartel, who is a leader in the field of RNA interference (RNAi). I really wanted to work on RNAi, and so I was mainly just looking forward to that and wasn't scared about the move to Boston. Then, the move to Seattle was smaller, since I was already in the US, and it felt natural because I was then excited to move into the field of chromatin evolution and holocentromeres.

After your stint in the US, you then moved back to Europe and started your lab at Institut Curie, Paris, in 2016. How did you find the transition from postdoc to group leader?

I tried to tell myself I was going to take it easy, because speaking to other postdocs who had made the transition, it sounded like they had quite a stressful start, like getting the lab equipped, for example. But I didn't want to stress about it, I wanted to try and enjoy it as much as possible and make the most of the opportunity; I think it's important to have that mindset. I also had good encouragement from the people here, including Genevieve Almouzni and Angela Taddei, who showed me that they liked the project and my ideas. There were also others who helped mentor me, especially with respect to the French research culture, which is a special one; it's quite different to other countries. For example, there is the CNRS, which is the French state research organization where you apply for a tenured position, so that your salary is covered. It can be complicated to understand for an outsider, but the people here really helped make it a positive experience and not too stressful.

However, when you are starting your lab, there is a lot of recruitment, and hiring people can be challenging. For example, you shouldn't hire someone if you have doubts, but the problem is that you always have them, and the difficulty is working out which doubts are the important ones. I think this is perhaps something that happened because we were never taught how to hire somebody. I can discuss this with other colleagues, but ultimately, I have to make the decision, which can be tough.

You mentioned the difficulties of hiring; what do you look for when choosing people to join your group?

I am obviously looking to hire someone who has a particular set of skills. But over time, I have come to realise that while the skills are important, another thing you have to consider is ‘can I work with that person?’. You have to be compatible with that person because unless you're in a really big lab, you will be directly interacting with them every day. As part of this, I think communication is very important, as well as your gut feeling. And if there's a candidate that doesn't have experience of a particular technique or set of skills in the lab, although it would be ideal if they could do them, they can always learn that and pick that up. But that natural relationship you build with someone you feel more comfortable with is harder to replicate.

What is the most important advice you would give to someone about to start their own lab?

Something I learned from my previous advisors is simply don't grow the lab too quickly. When you first start managing people, it already occupies a lot of time. Some people might be able to handle this more naturally than others, but you need to have time outside of that, because in the early stages, you are likely still doing a lot of experiments in the lab, and everybody says you are the best person in your lab at the beginning, because you're the one who knows the stuff. So, make sure you've got your foundation sorted and you're happy and comfortable with everything before taking on too many people.

What are the main questions your lab is trying to answer?

There are three main questions that I would like to try and answer. Firstly, I want to understand how and why centromeres are diverse, centromeres being the regions of the genome where kinetochores assemble and mediate chromosome segregation. The architectures and organizations are extremely diverse among eukaryotes, and we are working on a special type of centromere organization, called holocentromeres, where centromeric sites are distributed along the entire length of chromosomes. However, the ancestors of holocentric organisms were likely monocentric, where centromeres are restricted to one region, and so becoming holocentric is a really extreme evolutionary transition. Therefore, I would like to understand the mechanisms that underly this transition and get an idea why it occurred, although the ‘why’ is always a complicated question.

The second question that naturally interests me is about the mitotic organization of holocentric chromosomes. The centromere clusters on the surface of mitotic sister chromatids in eukaryotes. In holocentrics, this clustering is driven to the extreme as centromeres extend over the entire length of mitotic chromosomes. But what underlies this clustering and how this affects the organization of the mitotic chromatin, in particular in a holocentric, is an important question in the field.

Finally, the third question that evolved over the last two years is on the diversity of 3D genome organization. We don't know much about the diversity of spatial genome organization in eukaryotes in general, apart from the handful of model organisms, and neither do we really know how changes in the factors that drive or fold the genome might contribute to such diversity. However, the approaches used to study 3D genome organisation, such as Hi-C analysis, are expensive and require a lot of expertise for the analyses. So, I think this is quite a difficult project, but a very interesting one.

Your research involves working with Lepidoptera (butterflies and moths) and their larvae, silkworms – why did you choose Lepidoptera and what are the benefits or challenges of working with them?

When I thought about starting my postdoc, I was already interested in holocentromeres, and I read this review from Simon Chan on how holocentromeres have evolved in several different eukaryotic lineages, and I was quite surprised by how widespread they are. But people had already been researching holocentromeres in the model organism C. elegans, given that nematodes are also holocentric. So, I decided to choose a different organism, and I knew that Lepidoptera, in particular Bombyx mori (the silk moth), have cell lines and available genomic datasets that I could work with to map centromeres. In a worst-case scenario, we could just map another holocentric organism and produce a rather descriptive study. However, it turned out to be very interesting because Bombyx has lost the CENP-A histone variant that's essential for centromere function in other organisms, which raised additional questions and led us where we are today.

One of the benefits of working with Lepidoptera is that it's quite niche, with only a few labs working with Bombyx, and although other labs have some peripheral interest in their holocentromeres, we are the only lab really focused on this, so we are quite unique in that sense. Additionally, at the beginning, although the Bombyx genome was being sequenced, and also some other butterflies and moths, many other Lepidoptera were not. However, since the creation of the Darwin Tree of Life programme, which aims to sequence the genomes of many eukaryotes, the genomes of many Lepidoptera species are now available to us, giving us further insights into the evolution of genome organisations across Lepidoptera.

However, the main challenges of working with Bombyx are technical; because it is not a very well-established model organism, there are not as many tools available. Some tools are being established for Bombyx, especially in labs that we collaborate with in Japan, but everything is more challenging. For example, we cannot get CRISPR to work in the cell lines for an unknown reason. Additionally, we have to generate antibodies against all of our components because many commercially available antibodies do not work in Bombyx.

What is the best science-related advice you ever received?

Something that has always been emphasised to me is the importance of reading literature. Although results from the lab do determine the direction of your research, reading is also a great way of coming up with new ideas, complimented by discussing ideas with colleagues and attending conferences. And although it can be difficult to find the time to dedicate to reading, I think it's always rewarding, and you should try and make time for it.

You mentioned over email that working from home can be difficult with a family – what are your views on the feasibility of being both a good parent and a good scientist?

Of course, it is completely feasible, but you always struggle with the thoughts of ‘okay, I'm staying in the lab until 5pm, and I would love to continue this work now, but I have to go home’. So, even though you're excited by the science, you don't always have enough time for that. This can be particularly difficult in France at the moment, where there are lots of strikes, and so there are many more interruptions to scientific life, because suddenly you have to stay at home sometimes. Additionally, if I'm invited to attend a conference and I'm really thrilled about going, at the same time it means I'm going to have to leave my kids, which is sad. Also, logistically, it means I have to organise a babysitter and many other things in order to be able to leave to begin with. So, it is definitely feasible but there are a lot more considerations to make.

Finally, could you tell us an interesting fact about yourself that people wouldn't know by looking at your CV?

This is less of a fact and more of a story, but during my postdoc I lost a cockroach in the lab, and it was not a small cockroach, it was a Madagascan hissing cockroach, and these can be 10 cm in length; they're huge! We had them in the lab because I was isolating RNA from a variety of insects to do transcriptome assemblies. And so, when auditing these cockroaches, I had three of them in a box, and one minute they were all there, and the next, one of them had disappeared. At first, I thought perhaps my lab mates were playing a trick and having some fun, but it turned out it wasn't them. And on top of that, it turned out that the two remaining cockroaches were pregnant females. So, when I saw these other cockroaches giving birth to tens of small cockroaches, I thought, ‘okay, I'm going to be the one who is blamed for a cockroach infestation in the building’. In the end, the cockroach turned up on the back of a tip box that a student was using, and she was amazingly calm about it.

Ines Drinnenberg was interviewed by Daniel Routledge, Cross-title Reviews Editor at The Company of Biologists. This piece has been edited and condensed with approval from the interviewee.