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Kerstin Kleese van Dam

From left, Kerstin Kleese van Dam, Brand Development Manager at BNL Diana Murphy, and John Hill at the Practical Quantum Computing Conference (Q2B) in San Jose, CA, Dec. 2019. Photo courtesy of Kerstin Kleese van Dam

By Daniel Dunaief

Brookhaven National Laboratory is putting its considerable human and technical resources behind the global effort to combat the coronavirus.

John Hill, the director of the National Synchrotron Lightsource II, is leading a working group to coordinate the lab’s COVID-19 science and technology initiatives. He is also working on a team to coordinate COVID-19 research across all the Department of Energy labs.

“We are proud that the tools we built at BNL, which include the NSLS II, which took 10 years to build and cost about a billion dollars,” will contribute to the public health effort, Hill said. “We feel that science will solve this problem, and hopefully soon. It’s great that BNL is a part of that fight.”

In addition to using high-technology equipment like the NSLS II to study the atomic structure of the virus and any possible treatments or vaccines, BNL is also engaging a team led by Kerstin Kleese van Dam, who is the director of BNL’s Computational Science Initiative.

According to Hill, the combination of the physical experiments and the computing expertise will provide a feedback loop that informs the efforts with each team. Kleese van Dam’s team is using supercomputers to run simulated experiments, matching up the atomic structure of the viral proteins with any potential drugs or small molecules that might interfere with its self-copying and life-destroying efforts.

The computer simulations will enable researchers to narrow down the list of potential drug candidates to a more manageable number. Experimental scientists can then test the most likely  treatments the computer helped select.

Across the world, the scale of the science to which BNL is contributing is even larger than the Manhattan Project that led to the creation of the atomic bomb during World War II, said Hill.

In just three months since scientists in China produced the genetic sequence of the coronavirus, researchers around the world have produced over 15,000 research articles, some of which have been published in scientific journals, while researchers have self-published others to share their findings in real time.

Working with computer scientists from different fields at BNL, Kleese van Dam is helping researchers screen through the abundant current research on COVID-19. The number of papers is “accelerating at a rate no one can read,” Hill explained. 

Kleese van Dam and four of her scientists are setting up a natural language processing interface so scientists can type in what they want to find, such as a protein binding with a specific complex, and put it into a search engine. She is working on an initial service that she hopes to expand. Additionally, the computer science team is planning to start a project to look at epidemiological data to determine how various people might react to different treatment.

Kleese van Dam and her team are also working to build an archive in the United States that they hope will host at least the results of the Department of Energy funded projects in medical therapeutics. “[We are] convinced that this would provide a much better starting point for future outbreaks, as well as providing a near term clearing house of results,” she explained in an email.

As for the work at the synchrotron, Hill said that the high-energy x-rays can determine the specific atomic configuration of proteins in the virus.

The NSLS II, which was designed to study the structure of batteries, geology and plant cells, among other objects, can look at “small protein crystals better than anywhere else in the world.”

The virus relies on a docking mechanism that allows it to enter a cell and then insert its malevolent RNA to disrupt the cell’s normal function. Understanding how the pieces come together physically can allow researchers to look for small molecules or approved drugs that could interfere with the virus.

One of the many advantages of the synchrotron over protein crystallography is that the NSLS II doesn’t need as many copies of proteins to determine their atomic structure. Hill said protein crystallography needs samples that are about 100 to 200 microns in size, which is about the width of a human hair, which can take weeks to months to years to grow. This is a “bottleneck in the whole process” of solving protein structure, he said.

On the other hand, the NSLS II only requires samples of about a micron in size. This “greatly speeds up the process,” he added. Two different groups of researchers, from the pharmaceutical industry and from academia and national labs, are conducting experiments on the NSLS II.

Hill said he was receiving viral proteins scientists believe will bind with the virus from collaborators in the United Kingdom. The scientific process is as quick and collaborative as it’s ever been among researchers, he said. The proteins arrived recently.

That collaborative process would have “taken months to set up under normal circumstances,” Hill said. Instead, it only took a few days.

At the same time, BNL is constructing a cryo-electron microscope, which doesn’t have the same resolution as the NSLS II, but does not need crystals and can study individual proteins. Researchers need about 10,000 of them and can average the images together. The resolution is five to 10 times worse than x-rays.

BNL is accelerating the construction of the cryo EM and hope to have the first beam in mid-May. Commissioning will take some extra time, Hill said. The first structure of the coronavirus spike protein was determined by using an electron microscope.

For Hill and Kleese van Dam, who each have dedicated much of their time to these efforts, the opportunity to contribute to a project that could have implications for a public that is battling this disease is rewarding and offers reasons for optimism. 

“To be able to help at such a scale is indeed humbling and gratifying,” said Kleese van Dam. “Science is going to solve this problem,” added Hill. “That gives me comfort.”

Line Pouchard at the Great Smoky Mountains National Park in 2013. Photo by Allan Miller

By Daniel Dunaief

They produce so much information that they can’t keep up with it. They use the latest technology to gather data. Somewhere, hidden inside the numbers, might be the answer to current questions as well as the clues that lead to future questions researchers don’t know how to ask yet.

Scientists in almost every facility, including at Brookhaven National Laboratory, Cold Spring Harbor Laboratory and Stony Brook University, are producing information at an unprecedented rate. The Center for Data-Driven Discovery at Brookhaven National Laboratory can help interpret and make sense of all that information.

Senior researcher Line Pouchard joined BNL’s data team early this year, after a career that included 15 years at Oak Ridge National Laboratory (another Department of Energy facility) and more than two-and-a-half years at Purdue University. “The collaborations at the [DOE] lab are highly effective,” she said. “They have a common purpose and a common structure for the scientist.” Pouchard’s efforts will involve working with metadata, which adds annotations to provide context and a history of a file, and machine learning, which explores large blocks of information for patterns. “As science grows and the facility grows, we are creating more data,” she said.

Scientists can share large quantities of information, passing files through various computer systems. “You may want to know how this data has been created, what the computer applications or codes are that have been used, who developed it and who the authors are,” she said.

Knowing where the information originated can help the researchers determine whether to trust the content and the way it came together, although there are other requirements to ensure that scientists can trust the data. If the metadata and documentation are done properly “this can tell you how you can use it and what kind of applications and programs you can use to continue working with it,” Pouchard said. Working in the Computational Science Initiative, Pouchard will divide her time between responding to requests for assistance and conducting her own research.

“At Purdue, [Pouchard] was quite adept at educating others in understanding metadata, and the growing interest and emphasis on big data in particular,” explained Jean-Pierre Herubel, a professor of library science at Purdue, in an email. Herubel and Pouchard were on the research council committee, and worked together with other members to shepherd their research agendas for the Purdue University library faculty.

Pouchard “has a capacity to participate well with colleagues; regarding national and international venues, she will be a strong participating member,” Herubel continued. “She does well working and integrating with others.”

Pouchard recently joined a team that submitted a proposal in the area of earth science and data preservation. She has also worked on something called the Semantic Web. The idea, which was proposed by Tim Berners-Lee, who invented the World Wide Web, is to allow the use of data items and natural language concepts in machine readable and machine actionable forms. As an example, this could include generating rules for computers that direct the machines to handle the multiple meanings of a word.

One use of the Semantic Web is through searches, which allows people to look for information and data and, once they’re collected, gives them a chance to sort through them. Combined with other technologies, the Semantic Web can allow machines to do the equivalent of searching through enormous troves of haystacks.

“When I first started talking about the Semantic Web, I was at Oak Ridge in the early days,” Pouchard said. Since then, there has been considerable progress, and the work and effort have received more support from scientists.

Pouchard was recently asked to “work with ontologies [a Semantic Web technology] in a proposal,” she said, which suggests they are getting more traction. She is looking forward to collaborating with several scientists at BNL, including Kerstin Kleese van Dam, the director of the Computational Sciences Initiative and the interim director of the Center for Data-Driven Discovery.

Kleese van Dam has “an incredible vision of what is needed in science in order to improve computational science,” said Pouchard, who met the director about a decade ago when van Dam was working in England. Pouchard has an interest in data repositories, which she explored when she worked at Purdue University.

Living temporarily in Wading River, Pouchard bought a home in Rocky Point and hopes to move in soon. Her partner Allan Miller, from Knoxville, Tennessee, owned and managed the Disc Exchange in Knoxville for 26 years. He is starting to help small business owners and non-profit organizations with advertising needs. Pouchard experienced Long Island when she was conducting her Ph.D. research at the City University of New York and took time out to visit a friend who lived in Port Jefferson.

When she’s not working on the computer, Pouchard, who is originally from Normandy, France, enjoys scuba diving, which she has done in the Caribbean, in Hawaii, in Mexico and a host of other places.

When Pouchard was young, she visited with her grandparents during the summer at the beach in Normandy, in the town of Barneville-Carteret. Her parents, and others in the area, lectured their children never to go near or touch metal objects they found in the dunes because unexploded World War II devices were still occasionally found in remote areas. The environment on Long Island, with the marshes, reminds her of her visits years ago.

Pouchard has an M.S. in information science from the University of Tennessee and a Ph.D. in comparative literature from the City University of New York.

As for her work, Pouchard said she is “really interested in the Computational Science Initiative at BNL, which enables researchers to collaborate. Computational science is an integral part of the facilities,” at her new research home.