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Biophysicist in Profile

Sonia Longhi

Sonia Longhi

November 2016 // 4013

Sonia Longhi grew up in Milan, Italy. She dreamed of being either a medi­cal doctor, like her father, or a scientific researcher. After enjoying science in high school, she decided to enroll in the faculty of biological sciences at the University of Milan. “Very rapidly, I realized I was very interested by molecular aspects,” she says. She graduated with her degree in biochemistry in 1987 and then continued her training by pursuing her PhD in mo­lecular biology, which she completed in 1993. “During my PhD, I devel­oped an interest for structural modeling and, more generally, for protein structure,” she shares. “I therefore decided to make a postdoc in protein crystallography.” During her postdoc in the Architecture et Fonction des Macromolécules Biologiques (AFMB) lab, Centre National de la Recherche Scientifique (CNRS), and Aix-Marseille University, Longhi had the oppor­tunity to combine molecular biology, biochemistry, and structural biology and began acquiring an expertise in various biophysical approaches.

Following her postdoc, in 1999, she was recruited as a permanent senior scientist within the CNRS in the group of Bruno Canard, with a project focused on the structure-function relationships of proteins of the replica­tive complex of the measles virus. “I cannot tell you my disappointment when I realized that the CD [circular dichroism] spectra of the recombinant proteins, purified from E. coli, were typical of unfolded proteins,” she says. “A talented PhD student of mine, David Karlin, focused my attention on ‘natively unfolded proteins,’ as they were called at that time. That’s how I got started in the field. I decided to focus exclusively on protein intrinsic disorder. I fell in love with IDPs [intrinsically disordered proteins] and I thought that there was much more to grasp and to learn from studying IDPs than ‘classical’ proteins.”

Not everyone Longhi worked with shared this view. “From a scientific point of view, the big challenge [in my career] has been to convince my colleagues that intrinsic disorder was really biologically relevant and did not merely reflect an artifact of purification or a ‘curiosity.’”

In 2005, Longhi created her own group, Structural Disorder and Molecular Recognition, within the AFMB lab. Two years later she was promoted to director of research of class 2 and then in 2015 became director of research of class 1. As her career has advanced, she has found value in guiding the students and scientists working in her lab. “The most rewarding aspect to me comes from having the opportunity of supervising and somehow ‘forg­ing’ young, talented scientists that will be the next generation of PIs,” she shares. “Immediately after this, I would rank second the satisfaction of hav­ing my work published and hence accessible to the scientific community.”

As she moves forward, she hopes to continue contributing to her chosen field. “My plan for the future is to go on working in the field of protein intrinsic disorder and hopefully to contribute to a better understanding of the functional role of disorder,” she says. “If the funding context allows it, I would also like to focus on exploring the potential of IDPs for nanotechnology.”

Longhi has many role models in the field of IDPs. “My admiration goes to Keith A. Dunker, Vladi­mir N. Uversky, Peter Wright, and Jane Dyson, who have all been pioneers in the field. Without them, scientists would probably nowadays be deprived of the many joys that disorder brings,” she says. “They were the first to realize that intrinsic disor­der was abundant in the protein realm indicating that it probably plays an important biological role. They proved to be perseverant and most of all, not to be scared about defying paradigms. They finally were rewarded as the field has experi­enced a true burst. Thanks to all of them!”Longhi with her partner Frédéric Carrière, EIPL lab director at CNRS.

She also appreciates the role of the Biophysical Society in encouraging the growth of the field. “[BPS] played a crucial role in the development of the field of IDPs, in particular through the cre­ation of the IDP Subgroup,” she explains. “Given the prestige of BPS, this contributed to convinc­ing the scientific community worldwide that IDPs do exist and play important biological roles.”

Uversky, University of South Florida, has been a longtime collaborator of Longhi’s. “I knew about research conducted by Dr. Longhi well before I met her in person. In fact, I was very impressed by her studies on the structural and functional prop­erties of the intrinsically disordered tails of various viral proteins and often used results of these stud­ies as illustrative examples of what can be done by intrinsically disordered proteins,” he says. The two began collaborating after a few years of email communication, writing together, and co-editing two books: Instrumental Analysis of Intrinsically Disordered Proteins (2010) and Flexible Viruses: Structural Disorder in Viral Proteins (2012). “Dr. Longhi is a dream collaborator. She is a very nice person, kind, honest, and open-minded,” he says. “She is a great mentor who cares a lot about her colleagues and tries her best to ensure a bright future for them. The most useful thing I have learned from Dr. Longhi is that great science with some exceptional biological outputs can be done using rather simple systems. You just need to learn what to look for and how to look at it in order to see the big picture.”

Another of Longhi’s collaborators, Stefano Gianni, University of Rome, agrees that she is an excel­lent collaborator. “She is a dedicated scientist, clearly motivated by a genuine curiosity. She clearly devotes great attention to both the work and the human interaction arising from collabora­tion. Most remarkably, she is indeed an enjoyable person with whom it is always interesting to chat about anything in front of a glass of wine,” he shares. “She is humble and yet very knowledge­able and ready to hear the ideas of the youngest of the students with the same interest to those of the most senior professors.”

Dunker, for his part, offers praise for Longhi’s contributions to the IDP field. “Sonia has made many important scientific contributions to the growing field of IDP research. Her work is note­worthy for using multiple approaches for testing and retesting whether the region of interest has IDP characteristics, and thus her publications are very solid indeed,” he says. “Also, she has been very generous with her time, for example by organizing meetings and workshops and editing books, all of which provide substantial benefit to the IDP community.”

When Longhi is not working, she spends time with her family and participates in many sports. “I like swimming, jogging, dancing, skiing, and playing tennis,” she says. “I like making trails in the beautiful surroundings of Cassis, the small village close to Marseille where I live. I try to practice sport at least half an hour to an hour per day — I strongly believe in the Latin expression mens sana in corpore sano!

For those just starting out in their careers, Longhi advises, “Be perseverant, be quantitative, and don’t be afraid of challenging dogmas! It is only in this way that science can progress.”