Frequently Asked Questions

 

What does Cryo-EM stand for?

Cryo-EM is an abbreviated version of cryo-electron microscopy. Basically, the technology flash freezes samples (thus the CRYO/cold part). ELECTRONS are utilized to bounce around off the sample to form and image. And, MICROSCOPY, because this is all done on things smaller than the eye can see.

What are some of the first projects that will be focused on at HWI with the Cryo-EM technology?

HWI has been reaching out to regional collaborators like Roswell Park Comprehensive Cancer Center, the University of Rochester, and ZeptoMetrix as examples in hopes that they will be first to help us bring the instrument online and that the access will advance their research projects. Of course, the microscope is in very high demand within HWI as well.

Are there any specific examples of how this Cryo-EM technology helped researchers previously?

Structural biologists utilize a resource called the Protein Databank. When they determine what a protein looks like, they generally share that information freely with others to access worldwide to advance the rate and success of cures. Since the Cryo-EM instruments have improved so significantly in the last number of years, the number of protein structures ‘deposited’ to the bank has doubled and isn’t slowing down. The end result will be more cures at a quicker pace globally.ll.

What discoveries has Cryo-EM shown that have helped someone with a disease?

The Zika Virus gives us a wonderful example of how powerful this technology is. In 2016 when Zika became an international health concern, the virus was examined by a Cryo-electron microscope (Cryo-EM). Within 18 months because they were able to view the shape and structure of the virus, a vaccine was in clinical trial. What once would have taken decades, had impact on global human health in less than two years. Researchers across the world are now rapidly working to examine the corona virus with hopes to find a treatment and have already made great strides towards that because of Cryo-EM.

We have for decades known the protein responsible for Alzheimers, yet other techniques could not produce the essential structural data until now. As a result of Cryo-EM, we now know what the protein associated with the disease looks likes and can test people for it. This is just the beginning. Now that we can ‘see’ the protein that causes the disease, therapies are just around the corner.

What were scientists using before being able to use Cryo-EM?

Prior to Cryo-EM technology advancing to where it is now, the gold-standard technique for visualizing a protein was X-ray crystallography. This process, which requires coaxing proteins to form crystals, historically had its best success rates at 20%. Cryo-EM turns that on its head, and success is much more probable than failure for many of the samples important for health.  The advanced technology is successful more than 80% of the time.

How does the green energy battery project HWI is implementing work and how will it help the Center?

The storage device will be integrated with HWI’s building automation system and will charge itself during off-peak hours.  It is the first of its kind in NYS and has gotten support from Western New York Power Proceeds, National Grid and philanthropists.   HWI’s building technology will leverage the storage device to generate savings by reducing HWI’s electricity expenses.  As well the developers of the system and HWI will be working with the microscope manufacturer to see if the ‘clean’ electric coming off of the battery will improve the performance of the electron microscopes.

What would the Cryo-EM Center look like?

The Center is being constructed with a sample preparation lab, an instrument operator suite, three microscope rooms and a visitor center.  The Institute plans to bring on additional microscopes for the other two microscopes rooms as the Center grows.  Demand for time on these systems internationally far surpasses availability.  The visitor center, named for the James H. Cummings Foundation, will provide comfortable space for users to utilize while their experiments are running.  Specifically, the Center will be doing work for pharmaceutical organizations as well as regional academic and non-profit institutions.

How many researchers will be part of the HWI Cryo-EM Center?

The Center is being established with an initial team of four with plans to grow it to ten.  The UB Center for Computational Research is also involved in the project through the storage and protection of all of the data that the microscope generates.

When will HWI be getting the Cryo-EM microscope?

The first microscope is at HWI and is waiting for the Center construction to be completed before it is installed.  The microscope and the prep areas for experimentation are very unique in their heating, cooling, humidity and acoustic requirements.  HWI is working with numerous contractors to insure the ideal environment for this technology.

What are HWI’s hopes for this technology?

HWI for more than 60 years has set the foundation for cures to improve human health.  That is why we say CURES BEGIN HERE.  This tool adds to our ability to continue making meaningful contributions to alleviating disease as we have in the past in cases such as diabetes and cancer.  We want to see the next cure for breast cancer, Parkinson’s, or even leukemia, as examples, originate out of Buffalo.

How does Cryo-EM link research to clinical applications?

Structural biology with other techniques in the past often took a decade of effort to achieve meaningful results.  With the possibility of less than a 12 month timeframe to determine the structure of a protein and the very high success rates, structural biology results are now accessible to a far broader audience.  Research on the root cause of diseases will be greatly enhanced by the ability to now quickly and efficiently see what the ‘machines’ in our cells look like that are doing damage.  Once we know what their ‘blueprint’ looks like, we can design drugs to interact with them in the right way.  The end result is more cures, more efficiently.

What actions are being done by HWI to get the Center up and running?

We are working with NYS, local foundations and individual donors to weave a tapestry of support for the project.  We are still seeking support for many aspects of the project and would be happy for anyone to call our Development Director, Lisa LaTrovato, to see how they can engage.

The first microscope is here and the Center Director was recruited from the University of Florida to run the facility. Dr. Qiu-Xing Jiang has an impressive resume and studied for his PhD at Yale University. We are thrilled with his research accomplishments to date and are confident in how he will distinguish the HWI Center from others globally, as was the case when Herb Hauptman, HWI’s Nobel Laureate, was with the Institute.

Do many other organizations know about this technology?

Currently there are 60 centers in the United States and more are coming on line. There are international centers as well. The technology is so transformative that it has resulted in what the scientific community is calling the ‘Resolution Revolution’ as a result of the high quality images now being produced by this technology. HWI is proud to be bringing this resource to our region for the benefit of the BNMC and our regional community.

How can other organizations come in to use the technology?

The Center will permit proprietary access for small, medium and large pharmaceutical companies. Our regional partners, both academic and industrial, will have access to the facility in a process similar to what is done at national centers.  Projects will be given time on the instruments based good proposals.  Our own HWI teams will be working on their projects with the new center to push forward their discoveries.  There will be no short supply of users.

What is HWI’s long-term plans for this technology?

This technology builds on HWI’s strengths and complements our current research portfolio.  This new Center will collaborate with the HWI High-throughput Crystallization Screening Center as an example to build a more comprehensive structural biology resource here in Buffalo.

How many more microscopes would HWI like to have?

We are building space to accommodate 3 of these microscopes.  The instruments are so rapidly changing the landscape in discovering cures, we want to invest heavily in being at the front of this wave.

How long has HWI been working to acquire this machine?

HWI has been working for more than two years to bring this project to fruition.  We are grateful for the support of the community including New York State, foundations and individual philanthropists.  This Center and the results it will produce will be achievements to be shared by our entire community.

In years past, HWI has worked with friends and members of the community to understand that the results our teams produce would have impact on future generations to come.  Now, we can tell our dearest friends that the acceleration this technology presents will impact each of us today.

Why is this different than crystallography?

This is really the new frontier – with this new technology, we are able to speed up the process to discover new drugs. With cryoEM, we don’t need as much protein as we do with crystallography to determine the structures. This is especially useful for membrane proteins, which can be more difficult to produce and purify so you typically cannot obtain as much protein, and for those proteins where the structures simply cannot be determined by crystallography because of difficulty in growing diffracting crystals. In addition, cryoEM is more tuned for determining structures of large complexes, which may be very difficult to do using conventional crystallography.

How will this benefit people’s health?

CryoEM can accelerate the development of new therapeutic drugs. It can be integrated into the pipeline for developing small molecule drugs using the conventional tools. Our research programs and the projects to be pursued at the cryoEM center will impact a wide array of diseases, including Type II diabetes, cancers (i.e., pancreatic, prostate, lung), Alzheimer’s, Parkinson’s, ALS, and others.

What is the technology?

HWI is preparing to install its first high-resolution cryo-electron microscope this year. The microscope uses electrons to take pictures of individual protein complexes that are flash-frozen while in motion and utilizes high-power computers to calculate what these proteins look like from these pictures. HWI is also employing ground-breaking, sustainable energy technology to support the new microscopes. This will be the first such application of the lithium-based energy storage technology in New York State.

What is the economic development opportunity?

The cryoEM center is an opportunity to expand HWI’s research development and also make the technology available to a broad array of users and institutions locally and nationwide.  We can provide full-scale services to private-sector companies, educational institutions, and research groups.

What’s next?

CryoEM is still a rising phase of technology that will extend applications from molecular structures to subcellular or cellular structures to material sciences and chemical engineering. Its potential is not yet fully realized, making it a discipline rich in collaborative opportunities.