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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).

A Provost's Philosophy

trevor.kenney — Tue, 19 Oct 2010 17:51:38 +0000

Dr. Cheryl Misak (BA '83) never intended to go into academia. When she began her education at the ��Ѹ��Դ��߿�Ƭ of Lethbridge, Misak's goal was to become a lawyer.

As fate would have it (if fate does in fact exist – a question Misak has certainly pondered and discussed at length with hundreds of students over the course of her long and illustrious career) Philosophy 1000 was the only course that fit a gap in her schedule that first semester. You could say the rest is history, but in Misak's case, it's far more appropriate to ask whether certain things in life are just meant to be.

Taking a look at Misak's resumé, which brims with esteemed accomplishments, culminating in her current position as vice-president and provost at the ��Ѹ��Դ��߿�Ƭ of Toronto, it's easy to buy into the notion that things have a way of working out the way they should. That first course in philosophy that Misak added to her schedule simply out of practicality, set her life on an extraordinarily successful and interesting trajectory that she might not otherwise have pursued.

"I was immediately taken by it," Misak says of philosophy. "I agonized over what to do – it seemed that degrees in philosophy wouldn't lead to much of a career, but eventually I took the plunge."

Dr. Cheryl Misak (BA '83) was the 2009 recipient of the Alumnus of the Year award.

Misak followed her passion, earning a BA in Philosophy with great distinction, and the coveted Faculty of Arts and Science Gold Medal to go along with it. While she had her sights set on a Rhodes Scholarship that year, it was at Columbia ��Ѹ��Դ��߿�Ƭ that Misak earned an MA. Even so, Oxford was never off the radar. Misak reapplied for the Rhodes Scholarship while in New York, was accepted and went on to earn her PhD in England.

Since then, it's been one step after the other for Misak. She's been a lecturer at Oxford, graduate co-ordinator and assistant professor at Queen's, and then steadily moved up the ranks at U of T, advancing from professor to chair to dean to VP and principal – all the way to the top of the institution as vice-president and provost. It's an impressive succession that even Misak herself sometimes has trouble recognizing as her own career.

"It's a constant object of amazement to me," Misak says. "I had to be convinced to do each successive job. Each time I moved on, I found I was enjoying it more and more. People kept asking me to do things, and I just kept saying yes."

While the position of vice-president and provost at U of T is more than a full-time job, Misak makes a point of keeping her hand in research and teaching. She is currently working on research for a book titled The American Pragmatists – a subject matter very much in line with work Misak started while still an undergrad at the U of L. It is fittingly full circle – especially for a philosophy buff.

"Philosophy is about working through problems, getting to the bottom of things and trying to come to an understanding about concepts such as truth, knowledge, justice and the good. Ask a question about an old problem, and you're bound to learn something, if not new, then at least important."

The ��Ѹ��Դ��߿�Ƭ of Lethbridge Alumni Association Distinguished Alumnus of the Year award recognizes individuals for exceptional professional achievements, academic excellence or contributions to society.

2009 Distinguished Alumna of the Year

trevor.kenney — Wed, 07 Oct 2009 22:11:40 +0000

Dr. Cheryl Jayne Misak (BA '83)

Philosopher, scholar, and administrator, Cheryl Jayne Misak, is internationally renowned for her academic excellence. She graduated from the ��Ѹ��Դ��߿�Ƭ of Lethbridge with great distinction in 1983 with a Bachelor of Arts degree in philosophy and, in 1984, completed her master's at Columbia ��Ѹ��Դ��߿�Ƭ.

As the ��Ѹ��Դ��߿�Ƭ of Lethbridge's first Rhodes scholar, she attended the ��Ѹ��Դ��߿�Ƭ of Oxford and completed her doctorate in 1988, before beginning her career with the ��Ѹ��Դ��߿�Ƭ of Toronto in 1990 as a professor of philosophy. Endowed with natural leadership qualities, she has since held many administrative positions and brings a wealth of experience, expertise and wisdom to her current position as the ��Ѹ��Դ��߿�Ƭ of Toronto's vice-president and provost.

Misak has been interested in the philosophy of Charles Sanders Peirce since her first year at the ��Ѹ��Դ��߿�Ƭ of Lethbridge and has written and edited numerous articles and books that focus largely on his theory of truth. She is internationally recognized for her thought provoking, clear and challenging philosophical arguments and has been invited to speak at institutions and conferences all over the world.

Over the last few years, Misak has also been researching medical ethics. Her papers, published in the Journal of Respiratory and Critical Care Medicine, Chest and Critical Care, have notably impacted the profession.

Throughout her career, she has received many honours for her professional and academic accomplishments, including the Alberta Centennial Medal (2005), and was made a Fellow of the Royal Society of Canada (2001).

The ��Ѹ��Դ��߿�Ƭ of Lethbridge Alumni Association is proud to recognize Cheryl Jayne Misak as the 2009 Distinguished Alumna of the Year for her outstanding academic and professional achievements.

Athletics helped shape Misak's future

trevor.kenney — Wed, 14 Jan 2009 22:28:44 +0000

To attend or not to attend: that is the question — unless of course you are Interim Vice President and Provost at the ��Ѹ��Դ��߿�Ƭ of Toronto Dr. Cheryl Misak (BA '83). The question then, of course, becomes moot.

"My mother was a school teacher and it was pretty clear that we would be attending the ��Ѹ��Դ��߿�Ƭ of Lethbridge," remembers Misak. "Education was very important in our home."

It was a love of athletics, however, that would indirectly change the course of Misak's life. Born and raised in Lethbridge, Misak graduated from Catholic Central High School in 1979, and began attending the U of L with plans on becoming a lawyer.

"In my first term I wanted Fridays off so I could go on the ��Ѹ��Դ��߿�Ƭ's ski club trips and play in tennis tournaments, so I only chose Tuesday/Thursday classes," explains Misak. "I had one gap in my schedule and filled it with a philosophy class. I had no idea what philosophy was, but almost from the first day I realized that I really liked it."

Dr. Michael Kubara, Misak's first philosophy professor at the U of L, was very influential in Misak's education.

"He was great; he didn't mince words and was suitably hard on me. It was just what I needed. When I wrote a sentence that didn't make very much sense, he would tell me and then help me re-write it. He taught me how to write. Teaching someone how to write is teaching them how to think," says Misak.

A very dedicated student, Misak was involved in all manner of projects that went beyond the classroom. This gave her more than a valuable education that opened her thinking, but some administrative experience as well.

"At that time the Albertan philosophers would get together for a conference once a year. When it was Lethbridge's turn to host, I ended up doing a lot of administrative things that are unusual for a graduate student to do," recalls Misak. "Without graduate students to compete with, the keen undergraduates got a lot of attention. That was wonderful."

In 1983, Misak graduated with a bachelor of arts in philosophy with great distinction. She also won the Faculty of Arts and Sciences Gold Medal. Following graduation, she moved to New York City and earned her master's degree at Columbia ��Ѹ��Դ��߿�Ƭ. In her second year at Columbia, Misak became the recipient of a Rhodes scholarship, which eventually took her to Oxford ��Ѹ��Դ��߿�Ƭ in England.

"At Oxford I worked with fantastic people and met people from all over the world. I also met my husband there," says Misak.

She and her husband, Dr. David Dyzenhaus, taught briefly at Queen's ��Ѹ��Դ��߿�Ƭ in Kingston, Ont., before moving on to the ��Ѹ��Դ��߿�Ƭ of Toronto in 1990. Since the beginning of her career at the U of T, Misak has quickly moved up the ranks as professor of philosophy, Chair of the philosophy department, dean of the Missassauga campus of the U of T, acting vice-president and principal of the Mississauga campus, and then deputy provost of the U of T as a whole and into her current position.

Kubara is not surprised by her success.

"Cheryl had all-wheel drive with low range for plowing through the roughest going. She had a naturally disarming manner of getting her way," says Kubara. "While still at Oxford, her husband David and I predicted her destiny as a wonderful university administrator — a counter example to The Peter Principle."

It seems that Kubara and Dyzenhaus may have a future in fortune telling, because for Misak there seems to be no ceiling to her ascent.

GET THE FACTS

• Misak and husband, David, have two children, Alex and Sophie, and often travel together on sabbaticals to South Africa, England, Germany and New Zealand

• Misak's numerous academic awards include: U of T Student's Administrative Council Award; Alexander von Humboldt Research Fellowship; Recipient of five SSHRC Grants

• She has three published books and is currently writing another on American Pragmatism

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