Anne Bertolotti: Finding clues to combat neurodegenerative disease
Anne Bertolotti made an important career decision while she was still at school: she didn’t know what she wanted to do in life, but it had to be something that would keep its thrill; that would allow her to get out of bed every morning and be delighted to come to work. “Luckily, that’s what I have”, she says, “and I think that’s unique to science. As a child, I used to love Cluedo, solving mysteries, and there’s no better detective work than collecting clues about life and putting everything together at the molecular level.”
French by birth, Anne did a successful PhD in Strasbourg, purifying proteins involved in the initiation of transcription, something which she says was “trying to summarise life by protein-protein interactions”. Transcription is a basic property of all cells, but despite its importance, Anne knew that she wanted to work on something different – a physiological problem that she could dissect down to the molecular level. With her solid grounding in biochemistry, she realised that she could use her expertise to put molecular flesh on the bones of a vital cellular defence mechanism – the unfolded protein response pathway – which at the time was almost completely unexplored in humans. Accordingly, she went as a postdoc at the Skirball Institute in New York.
In just over two years of postdoc, Anne published six great papers, and succeeded, along with colleagues, in uncovering almost all the components of the unfolded protein response. When looking for her next destination, Anne says she had to ask herself a hard question: how was she to balance her desire for an exciting, challenging scientific career with her parallel wish to have a family? At that point, the answer lay in going back to France, to a permanent position in Paris. “I knew that in the French system I would have to start small, and work would proceed more slowly than it might have done elsewhere”, she says, “but the up side was that with tenure, I could embark on more challenging research, which often takes time. I could do the research I judged to be most important, without having to focus too much on the short term.”
Anne’s first child arrived shortly after her return to France in 2001, and she took four and a half months of maternity leave, focussing entirely on motherhood during that time. This might sound rather curtailed, but to someone just setting up a lab, it was a big step. “I enjoyed it and I had no guilt whatsoever”, Anne says. “What’s such a short time in a whole career? And I took longer for my second child!”
At first alone, and then with a small group, Anne began to work on how misfolded proteins contribute to Parkinson’s, Huntington’s and Alzheimer’s Diseases, the triple whammy of neurodegenerative disorders that stalk modern society, and by 2005, was successful enough that she was awarded a place on the prestigious EMBO Young Investigator Programme (YIP), designed to support the best young researchers in Europe.
It was at this point that Anne found, at an EMBO young investigator meeting, that the LMB had a job opening, through Sarah Teichmann who was then a group leader at LMB. This institution clearly suited her aspirations to work on long-term and challenging problems in an outstanding pluridisciplinary environment.
She came to Cambridge for the interview in 2006 accompanied by her husband and their second child, then a three-month old baby, circumstances that she says inadvertently became a test for how the LMB would perceive someone who wanted to be both a mother and a scientist. “I wanted to present myself for who I am”, says Anne, “and they handled it very professionally. I had regular breaks every three hours as my son was still nursing, and it was made very easy for me to incorporate that into the interview process.” The experience was also validation for Anne that she could be a mother and still compete at the highest levels: “I would never have considered doing such a thing – interviewing anywhere with a baby to take care of every three hours, let alone at the LMB – but I did it”, she says. “I think it’s a powerful message that shows that some of the barriers we think are impossible to surmount are in our heads. One just has to decide what’s important for oneself and go for it.”
At the LMB, Anne has carried on her work on how misfolded proteins contribute to neurodegenerative diseases. With her group, she interrogates cellular defence mechanisms to find clues to combat neurodegenerative diseases. Her lab has discovered several mechanisms that cells use as natural protection against misfolded protein, such as those accumulating in neurodegenerative diseases. In recent exciting work, her lab has been able to harness these cellular defence and discovered candidate drugs that selectively inhibit a phosphatase with key importance in allowing the cell to recover from stress. Inhibition of the phosphatase gives the cell more time to fix any misfolded proteins, and has been shown to improve outcome in a mouse model of Huntington’s Disease. The work is not only a breakthrough for Anne’s own field, but is the first time that phosphatases, a family of enzymes with vital importance in many cellular pathways, have been shown to be pharmaceutically tractable.
These days, as an established leader in her field – an EMBO member, a Fellow of the Academy of Medical Sciences, winner of numerous awards, and co-founder of a company developing treatments for neurodegenerative diseases – Anne has many calls on her time, but she says she has simple rules for deciding whether to accept invitations. “I like to be a good citizen but when I get requests to review people or grants or papers, I think whether it’s essential for me, with my particular expertise, to contribute, or whether there are ten or twenty other people equally qualified”, she says. And for meetings, she tries to say yes to invitations that will involve interacting with students, but otherwise picks and chooses very carefully, if possible suggesting lab members in her stead if she decides not to attend.
Anne is dedicated to giving her lab mentoring and support and she’s also “an active supporter of young women on the battlefield”, as she puts it, making sure that if she sees an excellent poster or talk by a young woman at a meeting, she congratulates the person concerned, and asks them about their career plans, giving them a pep talk if she sees they need it. She’s been known to follow up with the person’s lab head to ensure they know just how good they are.
But the problem’s not just with the younger researchers, Anne says. “We have to think about women’s careers in science from the PhD stage right through to the very top. We need to encourage junior women to apply to top-ranked places like the LMB, but we should also think about why so few of the successful female group leaders in any institution make it to the top of the tree. We don’t just want junior or middle-ranking women, we need women in leadership positions, and we still have a long way to go with that.” One way forward, she recommends, is rather than thinking about the “women in science problem”, one should focus on science done by women. Science speaks for itself, regardless of gender or background.
This article is based on an interview by Kathy Weston, February 2019.