Harvard Cryo-EM Center for Structural Biology


So my kids, they often bring me a toy that
they’ve broken, and the first thing I say to them is, ok,
let’s have a look at it and see if we can work out how to fix it. And essentially, structural biology is the
same. We’re trying to look at the inner workings
of the cell to find out how to repair it when things go
wrong. Knowledge of molecular structures is fundamental for developing new therapeutics and vaccines against cancer, neuro degeneration, emerging
infections, and many other diseases. And the best way to study those structures
is now cryo-EM. Cryo-EM is a transformative technology that
allows us to see tiny molecules at atomic level that
were impossible to visualize before. Most of the work behind cellular function is done by molecular machines made of proteins, and structural biology and cryo-EM allows
us to see these machines in enough detail so that we
can start understanding how they function and to start designing drugs that target specific
aspects of their function. My lab studies a cancer-causing protein called
BRAF. Most of my lab focuses specifically on viruses. It’s mutated in a number of cancers, but perhaps
most commonly in malignant melanoma. So for example we study eastern equine encephalitis virus, or triple E, which has been making the news recently because
of an uptick in the number of cases in New England and
neighboring states. So my lab studies how cells make proteins
and protein complexes and how they detect mistakes that occur along
these processes. So my lab is very interested to understand
how gram-negative bacteria develop their unique
cell wall. My lab studies a group of rare genetic diseases
known as ciliopathies. And trying to use this knowledge to develop
new antibiotics. Symptoms of ciliopathies include blindness,
respiratory disease, and infertility. So my lab studies circadian clocks. My lab studies protein molecules in the immune
system. We’re interested in how clocks are built,
what they’re made of, and how they drive 24-hour rhythms in cells
and in whole organism like us. So, using cryo-EM, we’re able to solve structures, such as the pore structure that I’m holding
right now. This pore structure allows us to understand
how the signal that induces inflammation is released
to the outside of the cell. We’re quite confident that understanding deeply
how this circadian clock functions will give us
a lot of practical information of importance to medicine. Because of the increased power of cryo-EM, we can begin to understand, in a very detailed
way now, how the BRAF molecule works. Obtaining this type of information is critical
to developing new drugs against infectious diseases
and cancer. Cryo-EM demands huge resources, both financial
and technical, and to make it possible, Harvard has teamed
up with the Dana Farber, Children’s Hospital, and the Mass General, to build a cryo-EM center that’s staffed with
extraordinarily talented experts. Cryo-EM has already transformed structural
biology and general biology research, and also will have a far-reaching impact in
drug discoveries. What really excites me about cryo-EM is that, as a structural biologist, it changed the
way in which I can think about problems. It completely transformed how we understand
biology and how we treat human diseases. It’s a new way of thinking, and it’s terribly
exciting.

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