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Rachelle Gaudet

The Department of Molecular and Cellular Biology is pleased to announce that Associate Professor Rachelle Gaudet has received tenure at Harvard University. Gaudet first came to Harvard in 1998 for postdoctoral work in Don Wiley’s MCB lab after completing her B. Sc. in Biochemistry at Université de Montréal, Canada and her Ph.D. in Molecular Biophysics and Biochemistry from Yale University. She joined the MCB faculty in 2002.

“I am absolutely delighted that Rachelle has agreed to stay on MCB’s faculty,” said Catherine Dulac, MCB Department chair.  “Her work on elucidating the structure of thermosensitive channels and membrane transporters is fascinating and extremely important scientifically. Not only will she be crucial in continuing to build on the departmental legacy, but she will also be a corner stone in strengthening x-ray crystallography in MCB. Rachelle is also an outstanding teacher and educator and has agreed to step in as the new head of the MCB concentration. In the name of the whole department, I wish to express my congratulations to a well deserved promotion to the position of Professor of Molecular and Cellular Biology.”

Richard Losick, who has worked closely with Gaudet as co-Head-Tutors in the MCB undergraduate concentration, also applauded the “most delightful news” about her tenure. “Teacher, colleague and scientist, Rachelle is highly valued member of our Department and the Harvard community. She is a constant source of insights and wisdom, and an excellent mentor both to undergraduate and graduate students who have worked in her laboratory. And I am in great admiration of her skills and intellect in bringing the methods of structural biology and biochemistry to bear on problems of fundamental importance in biology, such as the sensing of pain and temperature.  Finally, and not to be overlooked, Rachelle is simply the best Lindy Hopper in the entire scientific community!”

Channeling Pain
According to Markus Meister, Jeff C. Tarr Professor of Molecular and Cellular Biology and chair of the promotion committee, “what Rachelle does really well is to combine different methods to look at the same problem, and her choice of problem is inspired.” She studies the family of TRP (“trip”) proteins, which form channels in cells membranes and are important in sensing pain and heat – both from temperature and from chemicals like the capsaicin in hot chili pepper. Neuroscientists were very interested in these proteins, but had made little progress in understanding how they work. Gaudet took a unique approach for the field, using X-Ray crystallography to learn about the proteins’ structure and how the channels open and close in response to stimuli of different intensities. She also uses complementary biochemical methods to understand how they work in the cell.

Recently, she is studying how these channels adapt to their stimulus, becoming inactive, or desensitized, after some exposure. As Meister explains, “That’s why a Chinese dish might be frightfully hot at first bite, but by the end you’re really enjoying it. Rachelle has shown that it’s directly related to TRP proteins and how after they open, there’s a mechanism that closes them again.”A Hearing Link
What really fascinates Gaudet about the temperature-sensitive TRP channels is that they are sensory receptors that respond to physical rather than chemical stimuli. The theme of physical stimuli has brought her into collaboration with David Corey at Harvard Medical School to study “tip link” proteins involved in hearing, which also respond to physical stimuli: sound waves. These poorly understood proteins together form links between the cilia of hair cells in the ear.

Gaudet and Corey teamed up to resolve the crystal structure of one of the proteins, then used computer simulations that showed how the tip links behave under tension, when sound waves move the hair cells back and forth. They discovered that tip links provide mechanically strong, but also surprisingly stiff connections between cilia that hold the hair bundles together and impart mechanical sensitivity to the hear cells. Now, Gaudet and her team are looking at how different known mutations in tip link proteins undermine this mechanical strength and cause varying degrees of deafness. “The more we learn about how these proteins work, the better we can match a molecular defect to a deafness disorder,” she said.

Teaching and Mentoring
Gaudet loves research, but she gets just as much joy out of teaching and mentoring. Indeed, she has a remarkable track record of bringing undergraduates to her lab, where they shine. For one thing, it’s fun to work with capsaicin and menthol as part of neuroscience research on pain. But Gaudet also takes pains to provide projects that can grow with the students over several years and culminate in a senior thesis. “I like for students to be able to synthesize the data and present their results in a way they can be proud of.”

In addition to her role co-head tutor for the MCB concentration, Gaudet is a senior member of the department in structural biology where she spearheaded curriculum changes.

She is really happy to be able to stay in the department where she has made so many contributions. “I’ve enjoyed being able to invest lots of time in teaching and mentoring in an environment where people really care about it. I was worried that it would be anticlimactic to receive tenure. But it’s not!”

Now that she has cleared the tenure hurdle, Gaudet hopes to resume her competitive Lindy Hopping. But her previous dance partner has moved far away. Auditions, anyone?

For a previous profile of Rachelle Gaudet, see “Rachelle Gaudet is Hooked on Crystallography.”

[May 25th, 2011]

View Rachelle Gaudet’s Faculty Profile