Atomwise Partnership Enables UConn Researcher to Investigate COVID-19 Drug Target

University of Connecticut professor of molecular and cell biology James Cole* is working on identifying new therapeutics for COVID-19.

Through a collaboration with Atomwise, a California-based company which uses artificial intelligence to advance small molecule drug discovery, Cole is one of the 15 researchers looking at different coronavirus protein targets for COVID-19 treatment.

Cole is focusing on the NSP15/EndoU ribonuclease enzyme the COVID-19 virus needs to replicate as well as degrade viral RNA to hide it from host cell defenses. Cole is looking for a molecule that can inhibit the enzyme and thus inhibit replication of coronaviruses.

“The virus and the host carry out this war,” Cole says. “The virus has to evade the host’s innate immunity response while the host is trying to stop the virus from replicating.”

By inhibiting this enzyme, the body’s innate immune system would prevent the virus from replicating.

Atomwise is connecting researchers around the globe to their Artificial Intelligence Molecular Screen (AIMS) program. AtomNet, the company’s patented AI screening technology, screens millions of molecules to find those which have the highest probability of being useful for treatment.

Several other researchers at UConn have been recipients of AIMS Awards from Atomwise in the past.

AtomNet uses 3D models of various protein drug targets to identify molecules that may bind to them. Atomwise then sends these molecules to researchers who conduct experiments to find compounds that bind or inhibit drug targets.

Earlier this year, scientists published the structure of the NSP15/EndoU enzyme from SARS-CoV-2, the virus responsible for COVID-19, providing the basis for Atomwise’s analysis. Atomwise will search through its database to identify molecules which may bind to the surface of NSP15/EndoU and could potentially be used for drug development.

While there are many potential targets for COVID-19 treatment, NSP15/EndoU is particularly attractive because it is necessary for SARS-CoV-2 replication and is highly conserved among coronaviruses. This means this enzyme is very similar in all coronaviruses.

Successfully targeting NSP15/EndoU would block the virus’ ability to replicate without interfering with normal human cell function.

“There’s no close analog in humans, so it’s unlikely to inhibit things we don’t want it to,” Cole says.

This research may also have ramifications for other coronaviruses which are responsible for other illnesses including SARS and MERS as well as new, emerging coronaviruses.

In addition to partnering with Atomwise for virtual screening with AtomNet, Cole is utilizing UConn’s high-performance computer cluster and the Schrödinger Software Suite to perform additional molecule screenings.

Cole studies how a variety of viral pathogens interact with the host’s innate immune pathways, positioning him well to tackle the challenges presented by COVID-19.

“When the pandemic hit, I was beginning to think we can help with this,” Cole says.

Cole has applied for funding from the National Institutes of Health for this two-year research venture.

“It’s an exciting and new therapeutic target,” Cole says. “It’s a particularly good target and of scientific interest to me.”

 

*Dr. James Cole is a Professor of Molecular and Cell Biology, and is also a Joint Appointee within the Department of Chemistry at UConn.

Cole holds a Ph.D. from the University of California. He completed his postdoctoral training at Stanford University. His research focuses on using biochemical, biophysical and structural methods to define the key macromolecular interactions that regulate important biological processes, specifically the innate immunity pathway for defense against viral infection.


Article courtesy of Anna Zarra Aldrich, Office of the Vice President for Research

IMS Researchers Make Cover of Advanced Materials

May 26th Issue of Advanced Materials cover showing the work of Dr. Greg Sotzing and collaboratorsA molecular engineering principle in which repeat units of fairly rigid fused bicyclic structure and alkenes, separated by freely rotating single bonds, is proposed by Gregory A. Sotzing, Yang Cao, and published as a cover highlight of the May 26th Issue of Advanced Materials in article number 2000499, led by Dr. Chao Wu, a PDF at EIRC, and Ajinkya Deshmukh, a Polymer Program Ph.D. student for energy storage at elevated temperature.

The piston‐like crankshaft structure endows the system with a large bandgap of ≈5eV and flexibility, while being temperature‐invariantly stable. The piston/pendant allows engineering for temperature‐invariant dipolar polarization for energy storage. As part of a UConn lead MURI program, the design strategy uncovered in this work reveals a hitherto unexplored space for the design of scalable and efficient polymer dielectrics for electrical power and electronic systems under concurrent harsh electrical and thermal conditions.

Read More

 


Blurb courtesy of IMS News

UConn Researcher Invents Nanoparticle for Overcoming Leukemia Treatment Resistance

UConn associate professor of pharmaceutics Xiuling Lu, along with professor of chemistry Rajeswari M. Kasi, was part of a team that recently published a paper in Nature Cell Biology finding a commonly used chemotherapy drug may be repurposed as a treatment for resurgent or chemotherapy-resistant leukemia.

One of the largest problems with cancer treatment is the development of resistance to anticancer therapies. Few FDA-approved products directly target leukemia stem cells, which cause treatment-resistant relapses. The only known method to combat their presence is stem cell transplantation.

Leukemia presents unique treatment challenges due to the nature of this form of cancer. The disease affects bone marrow, which produces blood cells. Leukemia is a cancer of the early blood-forming cells, or stem cells. Most often, leukemia is a cancer of the white blood cells. The first step of treatment is to use chemotherapy to kill the cancerous white blood cells, but if the leukemia stem cells in the bone marrow persist, the cancer may relapse in a therapy-resistant form. Continue reading

Halle Barber ’20 (CLAS) Receives Outstanding Senior Women Academic Achievement Award

Halle BarberHalle Barber ’20 (CLAS) has been an undergraduate researcher in the Rouge Lab since her first year at UConn, starting in the Fall of 2016. During her first two years in the lab, she helped with the synthesis of lipoplex nanoparticles designed to mimic endosomes and participated in fluorescence studies focused on the ability of modified DNA to rupture the lipoplexes, a study for which she co-authored a paper in ChemBioChem (https://doi.org/10.1002/cbic.201800302). More recently, her research focus has been on the synthesis and design of a new DNA-based bioconjugation approach for crosslinking surfactant micelles. For this independent project she received the Chemistry Department’s 2018 Summer Research Fellowship, and the following year a 2019 UConn Summer Undergraduate Research Fund (SURF) award to continue her work. Also in 2019, Halle was the recipient of the 2019 LSAMP Fellowship Award which funded an opportunity for her to do research in Australia under the mentorship of Dr. Katharina Gaus at the University of New South Wales. Continue reading

The Journey to International Environmental Policy Starts with a Single Step

Penny Vlahos
Penny Vlahos, Assistant Professor of Marine Sciences

In the 1980s and 90s, concern about the destruction of the ozone layer was a topic on everyone’s mind. The international community rallied around the issue and the Montreal Protocol of 1987 was created to tackle the problem. As a result, the compounds causing ozone destruction, chlorofluorocarbons (called CFCs for short), were phased out. Since then, other international efforts have been undertaken to face other environmental crises, such as the Paris Agreement, the Rio Summit, and the Minamata Convention.

In the midst of the world-wide health crisis that is the COVID-19 pandemic, researchers continue forging ahead to identify steps to be taken to continue combating environmental threats and pollutants. Penny Vlahos, associate professor of Marine Sciences at UConn*, recently served on the scientific advisory panel for the International Panel on Chemical Pollution to advise United Nations policymakers on issues related to emerging environmental contaminants and pollution. The meeting was originally scheduled to be held in Zurich, Switzerland, but in light of the pandemic, was held virtually instead.

The path towards a protocol, treaty, or agreement – especially one like the universally ratified Montreal Protocol – can be a long and complex one. Vlahos shared her experience with UConn Today about some of the steps necessary to set plans into motion for tackling some of the world’s biggest environmental issues. Continue reading

LambdaVision/Birge Group Receives $5 Million from NASA

LambdaVision was awarded five million dollars from NASA to continue their work on the International Space Station (ISS) for an artificial retina that could help patients regain their sight. The award will fund flights to the ISS for the next three years to manufacture and improve the artificial retina technology previously developed by LambdaVision. The layer-by-layer process of producing the protein-based artificial retina requires less materials in a microgravity environment, reducing its cost and production time. In the future, LambdaVision hopes to begin clinical trials for their artificial retina technology.

LambdaVision was founded as part of the UConn Technology Incubator Program (TIP) and is spearheaded by Nicole Wagner (CEO) and Jordan Greco (CSO). Wagner and Greco are alumni of Dr. Robert Birge’s research group and currently serve as Assistant Research Professors in UConn’s Chemistry Department.

Read the full Business Wire article here.

Matthew Howell Awarded NSF Graduate Research Fellowship

Matthew HowellCongratulations to Ph.D. candidate Matthew Howell, the recent recipient of a prestigious NSF Graduate Research Fellowship. This fellowship will begin in Fall 2020 and continue through Spring 2023. Given the growing crisis of antibiotic resistant bacteria, Matthew—in collaboration with advisor Dr. Alfredo Angeles—is interested in examining the relationships between peptides, metal ions, and antibiotics. Together, they are searching for combinations that demonstrate synergistic killing of these bacteria.

“Outpouring of Support” as Researchers, Barnes & Noble Donate Lab Supplies to UConn Health

Labcoat
UConn Health is on the frontline of the response to COVID-19, and in need of supplies like those collected by Yashan Zhang and others at UConn. (Peter Morenus/UConn Photo)

“UConn is really my home,” said Yashan Zhang.

She lives in Farmington – just minutes from UConn Health – and she’s an assistant professor in residence in the Chemistry Department on UConn’s Hartford Campus. She’s also Chinese, though she’s been in Connecticut and part of the UConn community for the past 13 years.

“I started my PhD here in the Chemistry Department, and then I got my PhD and I got a job here,” Zhang said. “So I’ve been at UConn for a long time.”

For Zhang, it feels like the coronavirus pandemic has hit home twice: first, as it threatened her family and friends still living in China, and now, as its impact grows daily in the United States. It’s overwhelming for her at times – her voice fills with emotion when she talks about images of doctors forced to wear makeshift personal protective equipment, or to use the same protective mask for their whole shift. The daily reports of increasing positive cases of COVID-19 are tough for her to hear.

“Every day I see the numbers,” she said. “I always feel like, behind those numbers, they are actual, real people. That just makes me feel really sad.”

But like so many, it’s also empowered her to take action to help her neighbors and her UConn community – and her determination to help inspired a recent campus-wide effort to help support the doctors, nurses, and medical staff on the frontlines of the pandemic at UConn Health.

Continue reading

Research Spotlight: Following your scientific passion with Gregory Sotzing

Professor Gregory Sotzing
The University of Connecticut’s Professor Gregory Sotzing, who has developed different polymers like a color-changing fabric. Photo courtesy of Sotzing Research Group

Researchers from the University of Connecticut’s Sotzing Research Group are studying conductive and dielectric polymers for a number of applications, from color-changing fabric to medical applications of chemicals in cannabis to high-speed projectile launchers for the military.

The group is led by chemistry professor Gregory Sotzing. The group’s wide-ranging base of research is due to the number of applications for the polymers they study.

Sotzing explained that studying polymers really just means making new kinds of materials.

“We’re pretty much the people who make new materials, new compositions of matter. Then the engineers will take and test out these new things and see how well they work inside of certain kinds of applications,” Sotzing said.

Continue reading