Cyrus Moulton Telegram & Gazette Staff @MoultonCyrus

WORCESTER - Researchers have moved from the back row to the orchestra seats for the ballet of the cell, now that a new cryo-electron microscope is up and running at University of Massachusetts Medical School and attracting use and attention from all over the region.

Prior to this cryo-EM technology, it was like we were at the back of the arena with very poor vision, said Brian A. Kelch, assistant professor of biochemistry and molecular pharmacology at UMass Medical School. These microscopes now allow us to get 20/20 vision and move to the orchestra seats so we can now see all the dancers and see how they interact with each other. Then also when the dance gets out of synchrony, which could lead to disease, we can see how to bring those dancers back to synchrony which can fix that disease.

UMass Medical School held a ribbon cutting in October for a $12 million facility housing two powerful, high-resolution cryo-electron microscopes. The two microscopes - the roughly $5 million Titan Krios and the roughly $4 million Talos Arctica - will be the most advanced electron microscopes in New England and two of fewer than 50 such cryo-EM microscopes worldwide, according to Chen Xu, associate professor of biochemistry and molecular pharmacology and the core director of the Cryo-EM Facility at UMass Medical School.

The Titan Krios was acquired in collaboration with Harvard Medical School, supported by a grant of $5 million from the Massachusetts Life Sciences Center. The Talos-Arctica system was acquired with funding from the Howard Hughes Medical Institute. UMass Medical School has invested $3 million in renovations on its main campus to house the facility.

Now after lots of testing, calibration and training for staff, the Talos Arctica microscope is operational, and the Titan Krios is scheduled to come online this month.

The technology, known as cryo-Em, uses electron energy to produce images of samples that are cryogenically frozen with liquid nitrogen.

The technology not only allows scientists to see an object closer and more clearly than before but also allows scientists to see a sample frozen in many different positions.

Previous technology called X-ray crystallography required that samples be frozen in crystals that only allowed one position for samples. That process was also more time-consuming - it could take years to develop a sample, Mr. Xu said - and there was no guarantee that a sample that took so long to develop would be usable.

The new technology, however, can cut the time to develop a sample down to a month. It also requires less of a sample than the X-ray crystallography, according to Mr. Kelch.

Seeing the sample in multiple positions also enables two important developments.

It enables scientists to better reconstruct the sample in three dimensions and understand its function.

This is crucial for Mr. Kelch, whose lab is working on two projects.

In the first, he is studying the part of the cell that copies DNA and how that relates to cancer.

But without the cryo-EM, Mr. Kelch would not be able to look at the guardian proteins that are the target of the research. Although the study is in its infancy, Mr. Kelch hopes that understanding the structure of these proteins can lead to the development of chemotherapeutic drugs that work by interacting with the proteins.

In the second project, Mr. Kelchs lab is investigating how viruses become infectious particles. Again, being able to see the shape of proteins containing the virus is crucial to developing antiviral drugs.

Seeing the sample in multiple positions also enables scientists to discover how the sample can move.

Andrei A. Korostelev, associate professor of RNA therapeutics at UMass Medical School, described the process as like taking a picture of thousands of running horses and then arranging each horse in a sequence to show movement.

Here you freeze 1,000 horses, each of them moving differently, Mr. Korostelev said, continuing the analogy (the scientists actually freeze molecules). And then from that we try to reconstruct a smooth pathway of the movement.

Understanding movement is key to Mr. Korostelevs work studying the ribosome, the key machine in the cell that reads genetic code and converts it to proteins.

He has used cryo-EM to see how the parts of the ribosome move with respect to each other so the ribosome can perform its complex function.

Whats brand-new is that you can see the movements in such detail, said Mr. Korostelev, whose work has created movies of the ribosome in the process of making proteins.

But aside from their own research applications, scientists see the microscopes as a way to spark future collaborations among the different institutions and companies using the machines.

So far in addition to UMass Medical School, Harvard Medical School, Massachusetts General Hospital, biotechnology company Sanofi Genzyme and pharmaceutical company Vertex are some of the clients that are lining up to use the machine. The rates range from roughly $120 per hour for internal users to $300 an hour for industry partners, Mr. Xu said.

In addition, Mr. Korostelev said the microscopes are an attraction for students who are looking for the latest technology.

Mr. Kelch said the microscopes being at UMass is a boon for the entire state.

This whole facility can be an economic engine not just for academic science in Massachusetts, but also for the biotech industry as well, Mr. Kelch said. We get from them some money to help run the facility as well as make partnerships with those companies which helps our students and trainees to find new jobs once they leave here. The biotech industry gets access to the worlds state-of the art microscopes without having the burden of running that facility on their own. And all of that means a lot of growth, economic growth for the commonwealth.

Robert K. Coughlin, president and CEO of the Massachusetts Biotechnology Council, agreed.

It gives us a huge competitive advantage because this is state-of-the-art technology that is open source for many scientists to utilize, said Mr. Coughlin, whose organization represents more than 1,000 other organizations in the life-sciences cluster. If were going to continue in this region to be the best place for innovation, we need to stay ahead of the curve and constantly have access to cutting-edge equipment and technology.

Link:
Cyro-electron microscopes view 'ballet of the cell' at UMass Med School - Worcester Telegram