UNews - Tyler Mrozowich

��Ѹ��Դ��߿�Ƭ of Lethbridge researchers laying groundwork for the development of new antiviral treatments

caroline.zentner — Wed, 05 Apr 2023 21:56:30 +0000

Researchers in Dr. Trushar Patel’s Laboratory of Medicinal Biophysics at the ��Ѹ��Դ��߿�Ƭ of Lethbridge have revealed that certain viruses mediate RNA-RNA interactions and their findings lay a foundation for developing future antiviral treatments.

They studied a group of viruses known as Flaviviruses, which includes West Nile, Zika, Dengue and Japanese encephalitis. All of these viruses are spread by mosquitoes and, in most people, the illness is mild. However, in rare cases, West Nile can have serious neurological complications and Zika can cause birth defects and is linked to Guillain-Barré syndrome. The Japanese encephalitis virus is the leading cause of viral-caused encephalitis in Southeast Asia and the Western Pacific.

“Unlike humans who contain DNA as their genetic material, these viruses carry RNA as their genome and researchers hypothesize that one end of their genome needs to bind to the other end in order to replicate,” says Patel. “While evidence of these RNA-RNA interactions is available for some of these viruses, for others, like Japanese encephalitis, no experimental evidence exists.”

The ULethbridge researchers collaborated with the Wolfinger group at the ��Ѹ��Դ��߿�Ƭ of Vienna in Vienna, Austria and the Demeler group at ULethbridge’s Canadian Centre for Hydrodynamics. Using a variety of techniques, the researchers validated that a short fragment of the RNA genome is the primary driver of the RNA-RNA interaction that is critical for viral replication.

“Our work provides critical insights into the genomic interactions in this family of viruses,” says Tyler Mrozowich, a PhD candidate in Patel’s lab. “The integrated data analysis approaches we used can be adapted to study various viral and human RNA-RNA interactions to help us learn more about the role of RNAs in human diseases and viral infections.”

“As the RNA-RNA interactions are essential for the Flaviviral life cycle, this work lays the foundation for developing antivirals that would hinder the binding of one end of the viral RNA genome with the other end, thereby preventing their replication,” says Patel.

Their study, titled Investigating RNA-RNA interactions through computational and biophysical analysis, was recently published in Nucleic Acids Research.

New possibilities for therapeutic interventions revealed in collaborative study

caroline.zentner — Wed, 20 Apr 2022 22:12:08 +0000

Many medications on the market today target disease-related proteins, but a new study by scientists from Massachusetts General Hospital (Harvard Medical School), Merck Research Laboratories and the ��Ѹ��Դ��߿�Ƭ of Lethbridge has shown that small-molecule drugs can target non-coding RNA (ribonucleic acid), thereby expanding the possibilities for therapeutic interventions in many diseases.

“This work opens up the possibilities of developing drugs that can target RNAs that are involved with many diseases,” says Dr. Trushar Patel, Canada Research Chair in RNA and Protein Biophysics.

From left to right are Tyler Mrozowich, Dr. Trushar Patel and Dr. Maulik Badmalia.

In our bodies, DNA is transcribed or copied into coding RNAs, which in turn are translated into proteins that are the workhorses of a living system. However, most RNA is noncoding and scientists are learning about the critical role it plays in controlling systems. On a normal day, these nucleic acids provide cell maintenance and cell differentiation, but if they go rogue they can play a major role in diseases such as cancer.

Developing therapeutics against noncoding RNAs is very challenging, primarily because of their flexible shapes. Proteins usually have stable shapes and charged regions, meaning drugs can easily bind to proteins as a result. However, scientists know some regions of RNA have more stable shapes; the challenge is to find those regions.

After investigating thousands of small molecule compounds, the scientists at Harvard and Merck found one that binds to a specific noncoding RNA. To find out more about how the small molecule affects the RNA structure, the group turned to ULethbridge’s Dr. Trushar Patel, Tyler Mrozowich, a PhD student supported by NSERC, and Dr. Maulik Badmalia, a post-doctoral researcher supported by Alberta Innovates.

“We collaborated because we wanted to know what it looks like,” says Mrozowich. “Our lab specializes in visualizing these RNA molecules in solution. Our contribution was the visualization of this extremely important RNA element and we do this primarily through a technique called small-angle X-ray scattering.”

“This is one of the first examples of showing that RNA can be targeted for drug discovery, unlike traditional approaches where proteins have been targeted. This is a revolution in a way,” says Patel. “The second significant item is that we used a combination of various methods to come up with the full story.”

The methods used in this study could be applied in future studies to identify other drugs that target RNA.

“Essentially, the results of this study can also be translated as providing a platform for exploring new avenues for developing therapeutics in which RNA is involved,” says Badmalia.

The collaboration came about as a result of Mrozowich’s and Patel’s previous work with Dr. Karissa Sanbonmatsu (published in Nature Communications) at the Los Alamos National Laboratory, who also works with Harvard Medical School. The study was recently published in Nature, a leading science journal that has been in existence since 1869.

U of L students form first international chapter of the Biophysical Society

caroline.zentner — Tue, 22 Oct 2019 17:51:04 +0000

Graduate students in biophysics at the ��Ѹ��Դ��߿�Ƭ of Lethbridge have joined their counterparts at the ��Ѹ��Դ��߿�Ƭ of Montana in Missoula to form the first student Biophysical Society chapter in Western Canada, and the first that spans borders.

The connection across the Canada-United States border came about since one of the chapter sponsors, Dr. Borries Demeler, a U of L professor, is cross-appointed at the ��Ѹ��Դ��߿�Ƭ of Montana.

Tyler Mrozowich, a PhD student in Dr. Trushar Patel's lab, is the chapter's president.

“We wanted to create a partnership between these two universities and a way for biophysics students to communicate with each other, perhaps to talk about their research, the techniques they have available at each university and how each technique could help the students in their research,” says Tyler Mrozowich, a PhD candidate in Dr. Trushar Patel’s lab and chapter president. “Biophysics is a really under-represented subdiscipline in chemistry and biochemistry and physics as a whole. We want to highlight the different areas of research that biophysics is involved in and get people interested in the field.”

As Mrozowich explains, biophysics concerns the physical properties of biological molecules and how they interact.

“A really simple example is hemoglobin, the protein inside us that carries oxygen throughout the body,” he says. “The oxygen molecule will bind to the hemoglobin but the actual event where they interact, that’s biophysics. That is governed by physical properties of both of these molecules. In order for us to understand how it actually works, we have to study it and know how it interacts.”

Biophysics is an important element of health sciences research and is involved in everything from drug delivery and vaccine development to personalized medicine.

“Drug delivery is a very difficult aspect of medicine,” says Mrozowich. “It’s really easy to put a drug in a closed system and have it interact with a molecule. A lot of drug delivery fails because the body has so many methods of getting rid of the drug. Biophysics can help by determining the strength of interactions and how much should be given to a patient to get it in the right area or to exploit certain unique features of a target, like a cancer cell.”

So far, the club has formed an executive and has roughly 10 members. Membership in the club is open to anyone who’d like to join. Mrozowich says the club plans to bring in guest speakers to share their research and to participate in outreach initiatives that show the community, especially school students, how biophysics impacts daily life.

“When you think about sciences, you think about chemistry, biology and physics,” he says. “There’s so much more out there we want to get people excited about.”

Anyone interested in joining can email Mrozowich, Patel or Demeler.

Celebrating the versatility of ribonucleic acid (RNA)

caroline.zentner — Mon, 30 Jul 2018 16:51:26 +0000

Wednesday, Aug. 1 marks the first ever annual RNA Day, a celebration of the vital biological molecule, ribonucleic acid. RNA is a close relative of the commonly known molecule, DNA (deoxyribonucleic acid), and they, along with protein, are the three major biological molecules required for life.

Students at the Alberta RNA Research and Training Institute (ARRTI) at the ��Ѹ��Դ��߿�Ƭ of Lethbridge heard the call for an RNA Day celebration and they stepped up to host several activities in the community. They will be at the Downtown Lethbridge Farmers Market on Wednesday, Aug. 1 from 10 a.m. to 3 p.m., with fun kids’ activities, such as colouring and word searches, and the chance to talk to an RNA scientist.

Dr. H-J Wieden, bottom centre, works with students in the lab.

"I hope RNA Day shows the public more about research and how members of the scientific community are using RNA to try and better the lives of people, in a wide range of applications from medicine to agriculture," says Sydnee Calhoun, a fourth-year undergraduate studying biochemistry. "Since this is the first RNA Day, I hope we continue to build on this event for many years to come."

"I feel as though RNA Day is a great stepping stone towards making RNA knowledge mainstream,” says Jessica Semmelrock, another fourth-year biochemistry student. “I'm looking forward to the circulation of this knowledge, which I hope will bring the general public closer to the exciting research that is going on around them."

In addition to this free public outreach activity, ARRTI will also be hosting a livestream of a scientific lecture. The RNA Society and the organizers of the Ribosome Synthesis Conference have arranged for the keynote lecture by Dr. Ed Hurt (��Ѹ��Դ��߿�Ƭ of Heidelberg) to be shared live with the international RNA community. The talk is titled “Insights into the mechanism of eukaryotic ribosome biogenesis” and will be viewable at 6 p.m. on Wednesday, Aug. 1, in room C640 of ��Ѹ��Դ��߿�Ƭ Hall.

“RNA will play a critical role in the new age of biotechnology — the rational design and engineering of biomolecular-based systems and molecular machines,” says Dr. Hans-Joachim Wieden, the founding director of ARRTI. “The role of RNA in new and upcoming disruptive technology has been foreshadowed by the recent commercial successes of the CRISPR gene-editing platform and the emergence of RNA-based therapeutics and pesticides.”

An artist's rendition of an RNA strand

The field of RNA research has been expanding ever since it was identified as a molecule unique from DNA in the 1930s. Since 1957, there have been 31 Nobel Prizes for RNA Biology, with nine Nobel Prizes in Chemistry and 22 in Physiology or Medicine. In 1993, the RNA Society was formed to facilitate sharing and dissemination of experimental results and emerging concepts in RNA research. The RNA Society is a non-profit, international scientific society with more than 1,800 members. It hosts a peer-reviewed scientific journal (RNA), an annual scientific conference and is responsible for the declaration of Aug. 1 as RNA Day.

At the U of L, RNA research is flourishing within the ARRTI, with eight research groups and more than 100 trainees working on problems related to cancer, antibiotics, viral infections and agriculture.

“Many of the most-deadly viruses in the world have an RNA genome,” explains Tyler Mrozowich, a master’s student in the lab of Dr. Trushar Patel. “The study of this exceptional molecule will help us understand these viruses, and ultimately, help us combat the diseases they cause.”

“For me, the greatest outcome of RNA research is the development of RNA therapeutics,” says Chris Lindgren, another master’s student in the Patel lab. “To see someone’s face when they learn that they have been cured of a disease would make all the long days in the lab and the sleepless nights worthwhile.”

The significance of RNA research for the future of Canadians was recently endorsed by a $1.65-million training grant, jointly held by the U of L and the Université de Sherbrooke. The grant will allow these leading RNA-research institutions to develop the RNA Bioengineering and Innovation Network Collaborative Research and Training Experience (CREATE) to train job-ready leaders and innovators in the field of biotechnology.

UNews - Tyler Mrozowich

��Ѹ�����Դ���߿�Ƭ of Lethbridge researchers laying groundwork for the development of new antiviral treatments

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