Breakthrough discovery in U of L collaborative research study brings potential for new cancer therapies

caroline.zentner — Tue, 24 Jul 2018 16:23:10 +0000

Drs. Olga and Igor Kovalchuk at the ��Ѹ��Դ��߿�Ƭ of Lethbridge, in collaboration with researchers at Qiqihar Medical ��Ѹ��Դ��߿�Ƭ in China, the ��Ѹ��Դ��߿�Ƭ of Michigan and Boston ��Ѹ��Դ��߿�Ƭ, have shown for the first time that interactions between microRNAs, which are very small ribonucleic acid molecules, and transfer RNA (tRNA) can affect cell reproduction and cell death.

“This is the first time that anybody has shown such interaction is possible, that it is actually functional, that it regulates biological processes and also the processes that contribute to cancer,” says Dr. Olga Kovalchuk, a U of L biology professor. “These processes are pivotal for cancer because cancer cells get unlimited capacity to divide and no capacity to die. If you manipulate the levels of these RNAs, you affect these processes.”

The study, which was conducted over several years, was recently published in the Proceedings of the Natural Academy of Sciences of the United States of America (PNAS).

Deoxyribonucleic acid (DNA) contains genetic instructions used in the development and functioning of an organism. Genes tell a cell to make certain proteins. DNA and ribonucleic acid (RNA) work together to produce these proteins as part of a process called gene expression. RNA molecules can be of the coding variety, where they encode a protein, or the non-coding variety, which does not encode protein. Coding RNAs produce proteins that are involved in a variety of cellular processes, such as cell division, cell maintenance and cell metabolism, just to name a few.

“For a long time, we thought only coding RNAs were important,” says Kovalchuk. “But then it was discovered that there are small RNAs called microRNAs. They do not code proteins but they can interfere with the production of proteins. Sometimes, there may be a lot of RNA but the protein isn’t being produced because these small molecules are interfering. They are helping to fine-tune this process of gene expression.”

Scientists previously concluded that microRNAs only interact with coding RNAs called messenger RNAs (mRNAs) and interfere with full expression of genes.

“For quite some time, it was shown that only this specific interaction was possible, that microRNAs can only work with mRNAs,” says Kovalchuk. “By doing so, they can actually control cell division, cell death and malignant transformation. They are very powerful regulators even though they are small.”

Kovalchuk and her colleagues decided to examine one of the best-known microRNAs—a molecule called miRNA-34a which governs some key processes involved in cancer—and found it interacts with a small molecule —tRNAiMet — called initiator tRNA (transfer RNA) methionine.

“This was the first time anybody has shown that microRNAs can interact with other RNA molecules, especially tRNAs,” says Kovalchuk. “We had a lot of work to do to prove that the two actually interact with each other. It has functional consequences when this miRNA-34a interacts with tRNAiMet, affecting cell proliferation, cell-cycle arrest and levels of cell death.”

The study was conducted using a breast cancer model and the researchers are now looking at other types of cancers, specifically focusing on pediatric malignancies. Publication of the study opens the door to numerous other projects, including several articles already in the pipeline, and further collaborations.

“It has already started to garner attention and it will serve as a foundation for the big translational initiative, that is, taking results shown in a lab into a clinical setting,” says Kovalchuk. “If we show results with a couple of other cancers, we will have the potential to discuss the possibility of clinical trials and the therapeutic value of these molecules.”

U of L contributes to roadmap for enhancing human resistance to radiation for life in space

caroline.zentner — Thu, 10 May 2018 16:27:34 +0000

With more space exploration and possible colonization on the horizon, a group of international researchers, including the ��Ѹ��Դ��߿�Ƭ of Lethbridge’s Dr. Olga Kovalchuk, combined forces to produce a roadmap to enhancing human radioresistance, or the level of radiation an organism is able to withstand. The group recently published a paper exploring the subject in the peer-reviewed journal Oncotarget.

Earthlings enjoy natural protection from radiation thanks to the planet’s magnetic field and atmosphere but when they venture into space, radiation becomes a serious concern. In space, subatomic particles from the sun and other sources can tear through DNA molecules, splitting them or damaging the instructions they contain for cell reproduction, which can lead to cancers or other diseases. Astronauts receive some protection from their spacecraft but better shielding is needed for space missions that venture outside Earth’s magnetosphere, such as a trip to Mars.

“Space radiation affects gene expression in the entire body,” says Kovalchuk. “It affects epigenetic regulations, which are the underlying mechanisms that regulate gene expression. Gene expression is essentially the key machinery that underlies all biological processes in the human body.”

The team of researchers from NASA Ames Research Center, Environmental and Radiation Health Sciences Directorate at Health Canada, Oxford ��Ѹ��Դ��߿�Ƭ, Canadian Nuclear Laboratories, Belgian Nuclear Research Centre, Insilico Medicine, Boston ��Ѹ��Դ��߿�Ƭ, Johns Hopkins ��Ѹ��Դ��߿�Ƭ and many others collaborated to synthesize current information, identify the main hazards and ways of mitigating them, and propose further directions for exploration.

“There had never been an in-depth, systematic analysis of the health effects, possible outcomes, mechanisms behind these health effects and preventative strategies of exposure to radiation,” says Kovalchuk, a biology professor. “We want to be able to send people into space and have them as healthy as they are here. This is an example of a huge consortium working together and I’m so happy to have been a part of it.”

Space radiation exposure could affect the brain, cardiovascular system and the aging process. In addition to the need to find protective substances against radiation, research into daily regimens and geroprotectors, therapeutic agents that affect the cause of aging and age-related diseases, is needed.

Such research would also have applications for the aging population on Earth.

“We want to age in a way where we are active and healthy and productive,” says Kovalchuk. “Even though cosmic radiation is a bit of a different beast, what we learn from cosmic rays is still transferable. So, it will be pertinent for people in the nuclear industry, people who work with radiation on an occupational basis, and for me, as the Canadian Institutes for Health Research Chair in Gender, Work and Health, as we look at the health effects of exposure to occupational and environmental radiation. It may even be relevant to our radon exposures, which are very prominent in Alberta. A lot of what is learned can be applied here on Earth.”

UNews - Dr. Olga Kovalchuk

Breakthrough discovery in U of L collaborative research study brings potential for new cancer therapies

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U of L contributes to roadmap for enhancing human resistance to radiation for life in space

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