{"id":15624,"date":"2017-01-20T23:51:36","date_gmt":"2017-01-20T23:51:36","guid":{"rendered":"https:\/\/www.golive.clarku.edu\/news\/2017\/01\/20\/in-spratt-lab-students-learn-science-is-not-a-race-its-a-journey\/"},"modified":"2025-04-02T05:44:07","modified_gmt":"2025-04-02T09:44:07","slug":"in-spratt-lab-students-learn-science-is-not-a-race-its-a-journey","status":"publish","type":"story","link":"https:\/\/www.clarku.edu\/news\/2017\/01\/20\/in-spratt-lab-students-learn-science-is-not-a-race-its-a-journey\/","title":{"rendered":"In Spratt Lab, students learn ‘science is not a race, it\u2019s a journey’"},"content":{"rendered":"\n \n

With eye on medical breakthroughs, professor teaches undergraduates the ropes of biochemical research<\/p>\n \r\n\r\nOn the first floor of Clark’s Arthur M. Sackler Sciences Center<\/a>, behind a locked door in a darkened room, sits a $2 million scientific instrument that chemists routinely use to analyze the purity and chemical structure of molecules. It’s a nuclear magnetic resonance (NMR) spectrometer – a giant magnet enclosed in a 10-foot-high silver canister. Rarely found outside of larger universities or research institutes, the NMR spectrometer is one of the main reasons why Donald Spratt<\/a> joined Clark University’s Gustav H. Carlson School of Chemistry and Biochemistry<\/a> in August 2015.\r\n\r\n

\"Emilie
Emilie Ogisu ’17, pictured here with one of
Clark’s nuclear magnetic resonance (NMR)
spectroscopy instruments, has worked in
Professor Donald Spratt’s lab for 2-1\/2 years.
She’s now a fifth-year graduate student in biology.<\/figcaption><\/figure>\r\n\r\nThis high-field NMR spectrometer is a vital tool for Spratt and his students to conduct biochemical research that could have implications for future medical treatments involving chemotherapy drug resistance, childhood kidney cancer, Huntington’s disease, viral infections and abnormal fetal development. Outside of academic research, most people might encounter such technology in hospitals, which use magnetic resonance imaging (MRI) to create detailed pictures of a patient’s body for diagnosing physical ailments. MRIs use the principles of NMR and its methodology.\r\n\r\n“Honestly, I couldn’t be doing the research I’m pursuing without the NMR spectrometer,” says Spratt (above left, with undergraduate students)<\/em>, assistant professor of chemistry<\/a> and biochemistry<\/a> and Carl J. and Anna Carlson Endowed Chair in Chemistry. “At Clark, there are three NMRs, similar to what you would find at a much larger university. They’re readily available for us to conduct our research. And that’s invaluable.”\r\n

Studying ubiquitin, the ‘molecular ‘kiss of death’ ‘<\/h2>\r\nSpratt is a protein chemist and structural biologist who studies ubiquitin, a protein that earned its name because it is “ubiquitously” found in almost all tissues of eukaryotic organisms and is involved in regulating almost every biochemical pathway in the human body. His novel research program at Clark focuses on understanding how HECT E3 ubiquitin ligases properly attach ubiquitin to other proteins using NMR spectroscopy.\r\n\r\n“We want to understand the fundamental processes of how these enzymes work,” he says. “That’s where all these great leaps forward in drug development can happen.”\r\n\r\n
\"From
From left, Lara Prosterman ’17, Emilie Ogisu ’17 and
Pinky Htun ’17 purify proteins in the laboratory. Their
work in the lab last summer was sponsored via
Clark’s Interdisciplinary Summer Research Program;
they have continued to work in the lab this year.
Read more …<\/figcaption><\/figure>\r\n\r\nSince arriving at Clark, Spratt has welcomed numerous undergraduates — including 14 students this academic year — to join his research team. Each student chooses a protein to express, purify and characterize using the University’s top-of-the-line scientific equipment.\r\n\r\n“Each student gets their own protein to study and develops their own research project, with the ultimate goal of becoming a co-author on papers published in scientific journals,” Spratt explains.\r\n\r\nScientists discovered ubiquitin in 1975. In the 1980s, a research team from Israel and the United States — Aaron Ciechanover<\/a>, Avram Hershko<\/a> and Irwin A. Rose<\/a> — “figured out that ubiquitin was a molecular ‘kiss of death’ that the cell attaches to proteins it wants destroyed,” according to The New York Times<\/a>. In 2004, the three won the Nobel Prize in Chemistry for their “discovery of ubiquitin-mediated protein degradation.”\r\n\r\nSeveral years ago at an NMR conference in Australia, Spratt listened to the keynote address of an influential NMR spectroscopist who laid the groundwork for his work: Kurt Wüthrich<\/a>, who won the 2002 Nobel in Chemistry<\/a> for “his development of nuclear magnetic resonance spectroscopy for determining the three-dimensional structure of biological macromolecules in solution.”\r\n\r\nAs part of the next generation of scientists, Spratt is using NMR spectroscopy to study the underlying mechanisms that the HECT E3 ubiquitin ligases use to control the proper attachment of ubiquitin to specific proteins in the cell. Ligases create chemical bonds between molecules, in this case between specific lysine residues on a target protein and ubiquitin.\r\n
\"Graduate\r\n\r\nYaya Wang, a doctoral candidate in biochemistry and molecular biology<\/a>, works in the Spratt Lab and mentors undergraduate students. Read more …<\/a><\/blockquote>\r\n“There are 28 HECT E3 ubiquitin ligases in this family of enzymes encoded in the human genome. Four have been studied really pretty well; the other ones we don’t know much about. And all of them have disease relevance, which is why it is so important to understand how each of these enzymes work,” Spratt says.\r\n

NMR provides glimpse of proteins in action<\/h2>\r\nMany scientists study HECT E3 ubiquitin ligases using X-ray crystallography, a universal structural technique to determine the static arrangement of atoms in a molecular structure. To examine this family of enzymes, Spratt’s research team is employing both NMR spectroscopy and X-ray crystallography.\r\n\r\n“Crystallography is an excellent method to get a static snapshot of a protein structure, while NMR gives us the ability to look at the dynamics of a protein in solution,” Spratt explains. “By combining these methods, we can see the parts of the protein that are static and in motion, both of which are important to fully understand how these proteins do their job in the cell.”\r\n\r\nKnowing how the HECT E3 ligases work and behave, he believes, can lead to better targeting of drugs to treat certain diseases associated with HECT E3 ubiquitin ligase dysfunction.\r\n\r\nRecently, for example, Spratt was involved in a discovery as a research associate in the lab of Gary Shaw<\/a>, professor and Canada research chair in structural neurobiology at the University of Western Ontario<\/a>, in collaboration with Zhen-Qiang Pan<\/a>, a cancer biologist from the Icahn School of Medicine at Mount Sinai<\/a>. Using a high-throughput drug screen of drugs already approved by the U.S. Food and Drug Administration<\/a>, their international collaborative team discovered that the drug suramin<\/a> — which previously had been used only for treating African sleeping sickness — also has anti-tumor activity by inhibiting a key E3 ubiquitin ligase complex that controls cell division. The Proceedings of the National Academy of Sciences U.S.A.<\/a> published the findings last April.\r\n\r\nBecause Spratt’s research is so closely linked to such advances in biochemical research, he was attracted to Clark University and Worcester’s proximity to the booming biotech hub of Boston. And because Clark is a small research institution focused on teaching, he saw an excellent opportunity to involve undergraduates in his laboratory, giving them the chance to study these HECT E3 proteins.\r\n\r\n“I have them delving into the fundamental biochemistry of this family of enzymes,” Spratt says.\r\n

Students’ research has implications for cancer, other diseases<\/h2>\r\n
\"Emilie
“I want to go into oncology. This
lab experience will give me a better
understanding of why and how a
cancer cell develops.”
— Emilie Ogisu’ 17<\/figcaption><\/figure>\r\n\r\nLast summer, he supervised 10 undergraduates to work full time along with two graduate students in his lab. The undergrads received funding through Clark scholarships and fellowships such as Traina<\/a>, LEEP<\/a>, the Interdisciplinary Summer Research Program<\/a> and the James and Ada Bickman Chemistry Research Award.<\/a>\r\n\r\nTo identify which protein each wanted to study, “I had them read scientific journals and search through the online data repositories we have in our field.”\r\n\r\nAll the students continued their studies in Spratt’s lab this academic year, pursuing honors theses or individualized study on their proteins of interest.\r\n\r\n“The students overexpress their protein in bacteria, purify the protein, then they characterize their protein with different biochemical and biophysical methods with the top-of-the-line equipment we have here at Clark,” Spratt explains.  “We can study the secondary structure of the protein, look at the protein’s thermostability, measure the activity of the enzyme using various assays, and we can use the NMR spectrometer to examine the protein’s structure and dynamics.”\r\n
“Once you understand a protein’s mechanism, you can design better drugs, which can be used in future cancer treatments.”\r\n\r\n