UNews - RNA Research and Training Institute

Protein function discovery could advance antibiotic development

trevor.kenney — Mon, 24 Feb 2014 17:18:01 +0000

A new discovery made partly by ��Ѹ��Դ��߿�Ƭ of Lethbridge researchers could one day lead to more effective and efficient antibiotics, biofuels and other bioengineered products.

The discovery, partly by Dr. HJ Wieden's lab, could advance antibiotic development and everything from biofuels to laundry detergents.

The findings reveal a protein, YjjK, which helps a cell modulate protein synthesis by throttling, or pausing, the process when the cell is low on energy. Constricting protein manufacture enables a cell under these conditions to refuel with new nutrients to the point where it can restart the synthesis process.

“It’s very comparable to the energy-saver mode on a laptop computer, which shuts down energy-expensive processes when the battery is low to prevent it from crashing,” says U of L research-team lead Dr. Hans-Joachim Wieden, associate professor of physical biochemistry in the Department of Chemistry and Biochemistry, and director of the ��Ѹ��Դ��߿�Ƭ’s Alberta RNA Research and Training Institute (http://www.uleth.ca/research/alberta-rna-research-and-training-institute...).

The cellular function of YjjK was identified by research teams from the ��Ѹ��Դ��߿�Ƭ of Lethbridge and Columbia ��Ѹ��Դ��߿�Ƭ in New York, and they have since renamed the protein energy-dependent translational throttle A (EttA).

“EttA senses the energy state of the cell and, when needed, helps it save power by slowing down protein synthesis,” says Wieden.

Illustration by Anamaria Turuk

“This is the first time to show this particular type of direct regulation of protein synthesis based on a cell’s energy level. Our research provides a detailed understanding of a novel process related to cellular function.”

This new knowledge of EttA may make it possible to develop or improve antibiotics, since about half of them target protein synthesis as part of their function. Wieden says if an antibiotic can be designed to disable the EttA protein in a harmful bacterium, it would allow protein synthesis to continue unfettered and essentially burn out the bacteria’s energy supply.

“If you lose your energy regulation, you burn and crash – that’s a potential way to harm the bacterium,” says Wieden. “The ideal situation would be to come up with a novel class of antibiotics that haven’t been used yet.”

What the researchers learned when studying EttA’s role in E. coli bacteria is that when a cell is starved of energy, the protein interacts with the cell’s ribosome, a complex molecular machine that is the main site of protein synthesis, in a process called translation. This interaction inhibits the energy-intensive process of protein manufacture by preventing the progression from the initiation stage to the elongation stage of protein synthesis. The benefit to the cell is that it can curb energy consumption until more nutrients become available to boost the cell’s energy level, ultimately enabling the cell to resume protein synthesis.

In addition to the possible benefits this research could provide in the development of future antibiotics, Wieden says it could also enhance a variety of biotechnology products – everything from biofuels to laundry detergents – that rely on the efficient production of enzymes in microorganisms.

Their findings were featured in two articles earlier this month in the journal Nature Structural and Molecular Biology (February 2014 | doi:10.1038/nsmb.2740 & doi:10.1038/nsmb.2741).

U of L's iGEM Team claims two awards at World Jamboree

trevor.kenney — Fri, 08 Nov 2013 18:40:47 +0000

The ��Ѹ��Դ��߿�Ƭ of Lethbridge’s International Genetically Engineered Machine (iGEM) team captured two prominent awards at the iGEM 2013 World Championship Jamboree, Nov. 1-4 in Cambridge, Mass.

Fresh off claiming the top prize in the North American Jamboree in Toronto last month, the U of L team once again showed it was at the top of the North American class and continues to be one of the world leaders in the study of synthetic biology.

The U of L's iGEM student team consisting of (l to r) Graeme Glaister, Zak Stinson, Suneet Kharey, Jenna Friedt, Dustin Smith and Harland Brandon.

“I am very proud of the results they achieved on the world level,” says team leader Dr. Hans-Joachim Wieden, Director of the Alberta RNA Research and Training Institute at the U of L and Innovates Centre of Research excellence Chair of Bioengineering. “The World Jamboree was dominated by the European teams, but we presented very well and the awards we received were well earned.”

The U of L grabbed the Best Poster prize in the Overgrad classification, and also collected the Security Commendation, an overall award that debuted this year.

“I’m especially excited about the security award. It was brand new this year and shows how we are a world leader in this aspect of the research,” says Wieden. “The application of security protocols to the science of synthetic biology is becoming more and more important as we continue to advance the field.”

The U of L team’s project included the development of a bioengineering part that compresses genetic information – essentially working like a zip drive. Every gene needs DNA, but there is only so much DNA that will fit in a cell. This novel part may allow future bioengineers more flexibility in their work. Additionally, the team developed software that quickly determines what DNA is compatible to compress together.

Team member Harland Brandon said the research they conducted around the social implications of their project was lauded at the North American Jamboree and set their project apart from others.

“Our team sought to ensure that our part could not be misused to hide dangerous genes,” says Brandon (BSc’13), a first-year master’s student and Winston Churchill High School graduate. “We hypothesized that our part could be used to hide dangerous sequences, such as Ricin or Ebola, from gene synthesis companies. We then took it a step further and actually consulted with gene synthesis companies, U of L Risk and Safety Services and even a representative from the Federal Bureau of Investigations (FBI). Not only do we see our project benefitting the field, but we found through our critical analysis that the potential for misuse is not possible.”

Just six Canadian universities qualified for the World Jamboree, with the ��Ѹ��Դ��߿�Ƭ of Lethbridge and the ��Ѹ��Դ��߿�Ƭ of Calgary the only teams to capture awards.

iGEM is the premier competition for young scientists interested in the emerging field of synthetic biology, which is quickly leading to new discoveries that will diversify key economic sectors such as pharmaceutical, agriculture, medical diagnostics, clean energy and resource extraction.

“iGEM enables students to get their first taste of research,” says Wieden. “They understand the goal of the project, and learn how to think outside of the box, troubleshoot and apply their knowledge to create scientific discoveries. All of this unlocks students’ creativity.”

The ��Ѹ��Դ��߿�Ƭ of Lethbridge team consisted of Dustin Smith (BSc ’13), Graeme Glaister, Jenna Friedt (BSc ’11, MSc’13), Suneet Kharey, Harland Brandon (BSc ’12) and Zak Stinson.

To view full results from the iGEM 2013 World Championship Jamboree, see this website.

5 Questions with Dr. Ute Wieden-Kothe

trevor.kenney — Fri, 31 May 2013 22:32:24 +0000

Dr. Ute Wieden-Kothe joined theDepartment of Chemistry and Biochemistry at the ��Ѹ��Դ��߿�Ƭ of Lethbridge in 2006 after completing her PhD in biochemistry at the ��Ѹ��Դ��߿�Ƭ of Witten/Herdecke, Germany. Her research focuses on RNA (ribonucleic acid), an important molecule in life that resembles our genetic information, DNA.

Wieden-Kothe is particularly interested in understanding the complex functions of RNA in the cell which go far beyond encoding information. In particular, she investigates the formation of the cellular protein factories that are composed of RNAs and proteins. Wieden-Kothe is a member of the Alberta RNA Research and Training Institute (ARRTI), and every second year organizes the RiboWest Conference, which attracts hundreds of RNA researchers from across Canada. Her research is funded by NSERC, Alberta Innovates – Health Solutions and CFI.

Together with enthusiastic colleagues in the sciences and a number of science graduate and undergraduate students, Wieden-Kothe established the Let's Talk Science program in 2010 and now serves as the program's faculty supervisor.

Dr. Ute Wieden-Kothe, right, champions the notion of science outreach.

What first piqued your interest in your research discipline?

In biochemistry, we are investigating the molecular basis of life. In high school, I was absolutely stunned when I learned that we understand perfectly how glucose is broken down in our bodies to provide us with energy. I was deeply impressed that we can follow the fate of each atom of glucose until it is converted to water and carbon dioxide while ATP, the cell's fuel, is formed. It is amazing that science allows us to comprehend the world around us on such a detailed level. The idea fascinates me that by precisely understanding cellular processes, we might ultimately be able to address diseases at their roots, i.e. at their molecular causes, instead of "fixing" the symptoms of a disease.

How is your research applicable in the "real world"?

My research group studies the early steps of forming large machines in the cell, called ribosomes, which ultimately produce all proteins. Interestingly, ribosomes are composed of both proteins and RNAs which are intricately intertwined. By unravelling the assembly of RNAs and proteins, we want to obtain a better understanding of the formation of protein factories. Conducting this basic research is important for the real world in two aspects.

First, these protein factories are essential for rapidly growing cancer cells. Understanding how they are built will ultimately help to inhibit this process in cancer cells and allow us to find novel targets for cancer therapy. At the same time, it is our goal to identify the molecular cause of genetic diseases affecting formation of these protein factories. Second, we are learning how to construct novel molecular machines from RNA and proteins with unlimited functions and applications in nanobiotechnology, including nanomedicine.

What is the greatest honour you have received in your career?

I have received a couple of nice awards, such as the Minerva Mentoring Award and the CIHR Synapse Mentorship Award; however, celebrating students' successes together and seeing a student mature and grow is the greatest honour I can receive. It always fills me with joy when I observe how a student, who didn't quite know where he or she wanted to go, finds a passion and goal in research, science outreach or in teaching. Likewise, I am incredibly proud to help students push their boundaries, take on challenges and achieve more than they ever thought possible. I am at the university because of and for the students, and I am very happy when I can make a difference for these young people.

How important are students to your research endeavours?

Students are at the heart of my research program. Biochemistry is a highly collaborative and laboratory-intensive field where many sophisticated experiments have to be performed. This requires a team approach. Also as biochemical processes are often complex, we need year-round thorough discussions of all aspects of the question under study. The daily interaction with my students is thus the most important aspect of my research. I stop by the lab every couple hours to look at data, and every day I am sitting down with at least one student to have in-depth discussions. These conversations with my students are inspiring, creative, thorough and incredibly rewarding.

I am grateful every day to have a fabulous group of students in my research lab ranging from undergraduate to master's and PhD graduate students.

If you had unlimited funds, which areas of research would you invest?

First of all, I would support all areas of basic research to allow all of us to follow our imagination, to be curious and creative and to explore new ideas. The chances are very good that this basic knowledge will be useful in the long term. So many of our current technologies are based on such research in the past where nobody could envision today's applications.

Second, I would support all areas of science outreach to bridge the gap between research and the general public, in particular the next generation. We need to give children and youth the tools to expand their horizons, to better understand the world, to be confident to ask questions and to search for answers.

This story first appeared in the May 2013 edition of the Legend. For a look at the full issue in a flipbook format, follow this link.

5 Questions with Dr. Ute Wieden-Kothe

trevor.kenney — Thu, 16 May 2013 20:13:41 +0000

Dr. Ute Wieden-Kothe, right, champions the notion of science outreach.

What first piqued your interest in your research discipline?

How is your research applicable in the "real world"?

What is the greatest honour you have received in your career?

How important are students to your research endeavours?

I am grateful every day to have a fabulous group of students in my research lab ranging from undergraduate to master's and PhD graduate students.

If you had unlimited funds, which areas of research would you invest?

This story first appeared in the May 2013 edition of the Legend. For a look at the full issue in a flipbook format, follow this link.

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