Benedetta Bolognesi: "We have quantified all the mutations of the protein that causes Alzheimer's disease"

07/02/2024 - 20:18 h - Science Ajuntament de Barcelona

Interview by Àurea Grau for Barcelona Science and Universities and Núvol.

Benedetta Bolognesi is a biotechnologist and PhD in Chemistry from the University of Cambridge. During her postdoctoral stay at the Centre for Genomic Regulation (CRG) she studied the toxicity of some genes. Currently, and for the last five years, she has been the group leader of the Protein Phase Transitions in Health and Disease at the Institute for Bioengineering of Catalonia (IBEC), whose aim is to measure the effect of thousands of protein mutations and their ability to form different phases and cause toxicity in many neurodegenerative diseases such as Alzheimer’s, Parkinson’s and ALS.

What is your field of study, and what are your main lines of research?

The question is interesting because it is somewhat difficult to define what we do within a single discipline. We use genomics technology and strategies to understand the biophysics of proteins in human diseases. In other words, we try to understand how a protein works by analysing thousands of possible mutations in it. The main idea of our study is that if we see thousands of mutations, first, we will better understand how this mechanism works, and second, we will be able to pre-emptively anticipate how mutations will develop diseases in people.

What is your job as a researcher like?

In my day-to-day work as a group leader there is a lot of management in two aspects: managing the people in my team – knowing how they are doing, assessing how the experiments are going in the lab, looking at results together, etc. – and, on the other hand, managing the projects – how we are progressing in the study, publishing news, talking to collaborators, etc. There is also quite a lot of outreach work: writing papers, presentations and lectures, and reading everything that is published. But a very important part is writing projects to ask for money, this has been half of my work so far, and just a year ago we won the EU ERC Consolidator grant of two million euros to consolidate the research.

Is two million euros a lot of money for a laboratory, and what exactly does that translate into?

Two million for a junior laboratory is quite a lot. Research is expensive, and two million will fund the research of four people for five years. This gives us oxygen to work more, and we will be able to add another four or five people to the lab. We will grow.

What is the most important thing about leading a lab?

You have to be incredibly focused on the lab projects, reading, looking at the results many times, sitting down with the workers. Before, for example, I used to travel a bit more, but every time I try to choose better when and where I go, because every time I leave I lose that rhythm, and it’s hard to get it back. I prefer to give priority to these conceptual moments with the people in the lab, because they make the most sense.

Five years ago Núvol included you in a list of 25 outstanding women scientists in the country. How has your search progressed since then?

Five years ago I had an idea that might work and that was the idea that we could quantify the effect of each mutation in the protein that is deposited in the brains of Alzheimer’s patients. Now five years have passed, and it has worked, we have quantified the mutations, we know what they do, we know whether they will be pathogenic or not, and that has helped us a lot to understand the mechanism at the basis of this disease. And, on the other hand, it has given us the possibility of implementing this discovery with other proteins involved in other diseases. The fact that the idea has prospered has given the laboratory an identity, because it is what we do, and it has worked.

One of your latest works has been the development of the atlas of genetic mutations that cause the formation of a protein implicated in Alzheimer’s disease. What exactly does this involve?

We have generated the first mutational landscape for BETA amyloid, a protein that is deposited in the brains of Alzheimer’s patients. This means that we have quantified the effect of all possible mutations in this protein on its ability to aggregate, deposit and generate damage in neurons. Firstly, this has allowed us to know preventively or proactively what each mutation will do. This means that if you find a mutation in a patient or family that has nothing, you can already know whether this is a quiet mutation or a high-risk mutation. Secondly, when you generate a mutational landscape, you have a much better understanding of the mechanism at the basis of the protein aggregation process. This allows you to develop ideas that can inhibit protein aggregation and can be the basis for developing new therapies and strategies that allow us to reverse this process.

Do you think there is a lack of dissemination in the research world?

In the last five or ten years there has been a lot of publicity about new discoveries, but there is a lack of information about the process. What is published is the result of fifteen or twenty years of work by many people; there is a lack of more quantitative information about the facts. There is a lot of debate about science, but in the end there are very simple numbers that many people can understand. In day-to-day science communication, we should explain more of this quantitative information, so that people who are not scientists can get used to seeing a graph and know what it means. There are many opinions about science that forget the numbers.

What things have changed on a personal level in the last five years?

Personally, it has not been easy, it is necessary to have a lot of confidence and security, not so much in yourself, but in your ideas, knowing that what you are doing is important and worth the sacrifice. It is also very important to have mentors who believe in the project and can help you, because it is a very lonely job. Five years ago I didn’t know if I could do it, now I know I can do it, and that gives me a new energy that I can transfer to the lab.

What role has impostor syndrome played in this whole process?

The impostor syndrome was perhaps experienced in different situations from my early days as a Group Leader, each new situation was a challenge for the impostor syndrome. Now I have realised that I can do many things perfectly well, in the end it is experience that helps you.

Is research an easy profession to combine with motherhood?

Motherhood is for me what makes me disconnect from work, in my free time I am with my daughter. She is my work-life balance, because she makes me have a good dinner, she makes me stay at home and sleep, otherwise sometimes I would spend all day in the lab. The easy thing is that this job is flexible and if my daughter is sick, I don’t have to explain to anyone that I have to stay at home, that’s no small thing. Perhaps the most complex is not necessarily linked to science, but to the fact that neither I nor my husband are from here, and we have felt a bit lonely in the upbringing. My daughter is a girl and what was clear to me is that I didn’t want to tell her the story of: “I was doing all these important things, then you were born and that’s it”. Instead, I explain to her: “I was looking for it, I kept doing it, and you were born”. I wanted to be a role model for her and have my work and my identity apart from my identity as a mother. In conclusion, it is complex to be a scientific mother, yes, but conciliation is not a problem exclusive to science, it is complex to work and to be a mother because our society has not yet arrived here.

Did you want to be a researcher from an early age, and when did you decide to become a researcher?

When I was little, in a naïve way, I had the idea that I wanted to do something good for the world. When I started studying science in high school, and they explained to me what DNA was, I was captivated by these molecular mechanisms, the idea of life that you can’t see, but that is life. One day I remember there was news on TV about HIV and I talked to my father, who was a scientist but had never pushed me into this field, and he helped me understand that by looking for receptor inhibitors in HIV, new therapies could be developed for these people. From there I connected with the idea that by researching this tiny life that caught my attention, I could help improve the world.

Looking back over the last few years, do you think women are gaining ground in the world of research?

I see a lot of change in my lab, in my environment, in my students, but when you look up that change has not happened yet. It has not changed in representation, it has not changed in ways… I have seen things change a lot since I did my PhD fifteen years ago, when there was hardly any talk about it, even now I can ask my daughter, who is seven years old and is aware of the problem of women’s representation in science, and not because of me. There are more references. We are also going to be role models for the new generations, which gives us a lot of strength to endure within this system.

What advice would you give to a young female researcher considering a career in science?

My advice to a young researcher is to focus a lot on science, to learn new skills, not to be afraid to do difficult things. When you are young, you can do everything. I would advise her to focus more on science than on a career – the career is the consequence of good science.