Claudia Lengerke: "ERC is the right place to propose an innovative, more risky idea"

Firstly congratulations on receiving your ERC Consolidator Grant. Since the launch of the ERC in 2007, these grants have become one of the most highly recognized grants for researchers in Europe. Why did you decide to apply for an ERC grant?

I thought the ERC was the right place to propose an innovative, more risky idea. I had heard that the ERC promotes high-risk, high-gain proposals and felt it was right place for the project that I had in mind. As you look into the format in more detail, you realize that a solid experimental basis is required as well. I had an idea for an unusual project but I think it was important to also have some experimental evidence supporting my hypothesis

 An ERC Consolidator Grant was furthermore an opportunity to take my research group to another level. ERC projects provide stable funding over a five-year period, you have time to establish a new direction in your research andestablish methods that you don’t yet have in the lab. Importantly, it gives you time to take risks, as the immediate output that short term projects require is not as important.

Could you briefly explain the aims of your research project?

It is about subpopulations of leukemic stem cells that are resistant to current therapies and about understanding these subpopulations and the factors that make them resistant. These subpopulations are only a minority of cells but are thought to be responsible for disease progression and relapse in patients. By focusing on these unique cells, rather than on the whole population of cancer cells, we can learn a lot about what really matters for combating leukemia in patients. Scientifically these subpopulations are very interesting as they mediate all diseaserelevant events (emergence, relapse, therapy resistance). The ERC grant explores the hypothesis that, in order to survive, these cells need to colonize bone marrow niches and therefore compete with resident healthy hematopoietic stem cells. The grant explores howniches are populated by leukemic stem cells with specific focus on their competitive advantages over healthy hematopoietic stem cells. Niche colonization by leukemic stem cells should be inhibited by developing methods that give advantages tohealthy hematopoietic stem cells.We have a combination of basic research, where we look at a signaling pathwany in healthy and leukemic stem cells and proof-of-concept research that could potentially be applied in the clinic. An unbiased screening using zebrafish models could provide unsuspected angles. Further exploration in murine models and human cells may provide a basis for clinical translation. I think that this is indeed a high-risk high-gain project, that goes from basic models such as zebrafish and mice to patients, and thus bridges the gap between basicand clinically-oriented research.

The ERC evaluation criteria request ambitious, high-risk high-gain projects. How did you address this in your proposal?

The hypothesis of the proposal is provocative, because we aim to fight leukemia by targeting healthy stem cells, instead of the disease-causing leukemia cells themselves. We explore how the modulation of healthy hematopoietic stem cells can enhance their competitive advantages over leukemic stem cells for niche occupation. Leukemic stem cells are thus moved out from protective bone marrow niches, and thereby become targetable by conventional therapies. Fighting leukemia by targeting healthy stem cells instead of leukemic cells is a very novel idea that goes away from the mainstream of research and there is a potential high-gain for the treatment of patients suffering from leukemia. If we can combine such new therapies with current treatments we could enhance cure rates and long-term healing. We have the tools here in Basel for stem cell transplantation, so if our research proves successful, we canmove on to applying this clinically. Perhaps we also learn something about cancer in general, the project is about leukemia but other cancers also take advantage of niches, so perhaps we stumble upon knowledge that could be useful beyond leukemia.

ERC proposals are evaluated in 2-steps. Can you tell us what in your opinion is the most important factor for reaching the second round of evaluation?

I put a lot of energy into preparing the step 1 proposal. My strategy was to reach step 2, in order to learn about the process and receive feedback on the full proposal. Reaching step 2 would also have given me a chance to re-apply directly in 2020, which for me would have been the last year I could apply to the Consolidator category. I think the five-page synopsis is the most important part, as it allows you to move on to the next step and either receive the funding or learn about the process and get feedback from the evaluation panel. It is important to prepare yourself, to learn about the format of the proposal and to understand who is reading your proposal. It’s not just about therigorous science but also about explaining your idea well, why it is important to the field and why it has the potential for scientific breakthrough. The panel has quite diverse  expertise, so you need to also give a broad overview, and try to not be too technical.

Being a professor, clinician and a successful researcher is an incredible portfolio to juggle. How did you plan the preparation of your proposal? How much time did you dedicate to proposal writing?

I had the project idea on my mind for some time but felt that it was too provocative to be submitted in a conventional grant formatThe high-risk high-gain format of the ERC projects, seemed to be the right fit. However, I was intimidated by the reputation of the ERC. Through comparing myself to current ERC grantees and talking to colleagues, last year I finally felt that my CV and track-record were at the stage where I could give it a try. It is difficult to decide when to applybut at some point you have to take the leap and try. I still had an additional year where I would have been eligible for the Consolidator category. For me, having one additional potential chance after my propsal also took away a bit of the pressure.

You have to prepare yourself well and it takes time. You need to take time out of the daily routine. I shut myself away in the office, put other things aside and concentrated on the proposal. It was hard work and reminded me of my days as a medical student. Ideally, you should go to the mountains to write or plan a sabbatical but this isn’t always possible.

For me the idea was already set but if you need to shape the idea, you need to think out of the box and to explore new avenues. For inspiration, you could go to conferences or talk to people who are outside of your direct field. Once you have the idea, do some initial experiments to substantiate your hypothesis.  

What is the biggest challenge in writing an ERC proposal?

After having the right high-risk high-gain project idea, I think understanding the format is very important. It is a bit different to other funding schemes, in some ways it is less detailed and more focused on the big picture. Look at the documents and templates carefully, go to the information events, ask colleagues who have been successful with such grants for advice. The proposal needs to be high-risk but with a solid basis and this is a contradiction in terms, being able to bring this together in one project is the biggest challenge. My project has three individual tasks but they are strongly linked together. I started with the most solid task and built  the more risky parts around it, to form a complete project. I think the nice thing about the ERC format is that it makes you think about your research as a whole and where you want to take it in the future.

Your proposal was successfully chosen for the second round, this in itself is a great achievement. How did you prepare for the interview in Brussels? Can you tell us a little bit about the procedure and how the interview went?

I invested a lot of time in preparing for the interview.I held my talk in front of experienced colleagues from different fields, who were familiar with the ERC grant selection procedures, to test whether I presented clearly enough and to get input on potential questions. I am very grateful for their very helpful suggestions. At the same time, I tried to stay relaxed about it. I was happy to be accepted into the second round and saw it as a learning experience. They asked questions from a lot of different angles and they asked tough questions. They want to see your drive, independent thinking, and motivation to pursue the questions in your proposal. They want to see that you are totally committed to your project and believe that you can implement it.

Thank you very much for this informative interview, Claudia!