Preventing colorectal cancer and stillbirths

Characterizing a tiny protein—determining its shape and what it does—was the first step taken by Dr. Kirsten Wolthers and her colleagues in their effort to learn more about a very common molecule that is implicated in a wide range of human ailments.
Wolthers used the Canadian Light Source (CLS) at the University of Saskatchewan to study flavodoxin. This protein is produced by all sorts of bacteria and some algae, she explained, including the bacteria associated with influenza, H. pylori, E. coli and even appendicitis.
Of particular interest to the associate professor from the University of British Columbia is the flavodoxin produced by Fusobacterium nucleatum, an oral bacteria found naturally in the human mouth that plays a role in periodontal disease and gingivitis.
“What makes it so interesting is that what’s been emerging in the last 10 years or so are links between F. nucleatum and colorectal cancer and pre-term or stillbirths,” she said. In some studies, mice given oral F. nucleatum have shown a higher-than-normal incidence of pre-term births. Because flavodoxin is known to be essential for the lifecycle of the bacteria, it is seen as a potential target for a controlling growth of the bacterium.

> Read more on the Canadian Light Source website

Image: Dr Kirsten Wolthers working in a laboratory.

Revolutionary discovery in leukemia research

Leukemia affects over 6,000 Canadians per year. A team of researchers used the Canadian Light Source (CLS) at the University of Saskatchewan to discover a new way to kill leukemia cancer cells. When the scientists hyperactivated the “garbage disposal systems” of leukemia cells, it caused the cancer to die.
The researchers believe this finding will transform the direction of cancer therapy by focusing on a protein that was previously believed to be impossible to target. Their study was featured on the cover of the journal Cancer Cell.
“It was a major advancement to visualize the structural biology through crystallography facilities at CLS and to prove conclusively that ONC201 binds and hyperactivates ClipP proteases to induce cell death,” said co-author Dr. Aaron Schimmer from the Princess Margaret Cancer Centre and the University of Toronto.

>Read more on the Canadian Light Source website

Image: Interface of two heptamer rings in an apparently closed conformation of human mitochondrial ClpP.

Helping people to hear

Using advanced techniques at the Canadian Light Source (CLS) at the University of Saskatchewan, scientists have created three-dimensional images of the complex interior anatomy of the human ear, information that is key to improving the design and placement of cochlear implants.
“With the images, we can now see the relationship between the cochlear implant electrode and the soft tissue, and we can design electrodes to better fit the cochlea,” said Dr. Helge Rask-Andersen, senior professor at Uppsala University in Sweden.
“The technique is fantastic and we can now assess the human inner ear in a very detailed way.”
The cochlea is the part of the inner ear that looks like a snail shell and receives sound in the form of vibrations. In cases of hearing loss, cochlear implants are used to bypass damaged parts of the ear and directly stimulate the auditory nerve. The implant generates signals that travel via the auditory nerve to the brain and are recognized as sound.
By imaging the soft and bony structures of the inner ear with implant electrodes in place, Rask-Andersen said the researchers were able to discover what the auditory nerve looks like in three dimensions, and to learn how cochlear implant electrodes behave inside the cochlea. This is very important when cochlear implants are considered for people with limited hearing.

>Read more on the Canadian Light Source website

Image: the inner ear

Scienstists make breakthrough in creating universal blood type

Enzymes in the human gut can convert A blood type into O.

Half of all Canadians will either need blood or know someone who needs it in their lifetime. Researchers from the University of British Columbia have made a breakthrough in their technique for converting A and B type blood into universal O, the type that is most needed by blood services and hospitals because anyone can receive it.
In a paper published in Nature Microbiology, Stephen Withers and a multidisciplinary team of researchers from the University of British Columbia show how they successfully converted a whole unit of A type blood to O type using their system.  They were able to remove the sugars from the surface of the red blood cells with help from a pair of enzymes that were isolated from the gut microbiome of an AB+ donor.
The Canadian Light Source (CLS) at the University of Saskatchewan (UofS) played a critical role in understanding the structure of a previously unknown enzyme that was part of this pair. The researchers were unable to identify what this unique enzyme looked like from the gene sequence they had.  Crystallography, done at the CLS, was crucial for the researchers to understand how this enzyme works and why it had a particular affinity for the A type blood.

>Read more on the Canadian Light Source website

Improving engine performance and fuel efficiency

A study conducted in part at the Canadian Light Source (CLS) at the University of Saskatchewan suggests reformulating lubricating oils for internal combustion engines could significantly improve not only the life of the oil but the life of the engine too.
Dr. Pranesh Aswath with the Department of Materials Science and Engineering at the University of Texas at Arlington and his research colleagues focused on the role soot plays in engine wear, and its effect on the stability of engine oil.
He described the research as “one piece of a broader story we’re trying to write” about how the reformulation of engine oils can reduce emissions, decrease wear and increase the longevity of engines.
Soot is a carbon-based material that results from incomplete combustion of fuel in an internal combustion engine, he explained. The soot ends up in crankcase oil where it is trapped by additives, but that leads to reduced engine efficiency and a breakdown of lubricating oil.

>Read more on the Canadian Light Source website

Keeping nuclear power safe

Nuclear energy is clean, powerful, affordable, and zero-emission. A new study uses the Canadian Light Source (CLS) at the University of Saskatchewan to help ensure that waste from nuclear power plants remains safe and secure for thousands of years to come.
The project, led by Dan Kaplan and Dien Li, researchers at the Savannah River National Laboratory in South Carolina, looks at storing iodine, which is generated during uranium use, including in nuclear power generation.
Among the challenges of iodine management is its slow rate of decay—it has a half-life of 16 million years. Iodine is volatile and highly mobile in the environment, making containment critically important in nuclear waste management.
Currently, nuclear waste disposal sites use Ag-zeolite to sequester iodine from nuclear waste streams, which is then encased in concrete to prevent leaching.

>Read more on the Canadian Light Source website

Image: Samples of different formulations of cement that were tested for their ability to immobilize radioiodine.

Scientist discover that charcoal traps ammonia pollution

Discovery could have implications for agricultural management and climate change mitigation

Cornell University scientists Rachel Hestrin and Johannes Lehmann, along with collaborators from Canada and Australia, have shown that charcoal can mop up large quantities of nitrogen from the air pollutant ammonia, resulting in a potential slow-release fertilizer with more nitrogen than most animal manures or other natural soil amendments. The results were published Friday in Nature Communications.

Ammonia is a common component of agricultural fertilizers and provides a bioavailable form of the essential nutrient nitrogen to plants. However, ammonia is also a highly reactive gas that can combine with other air pollutants to create particles that travel deep into the lungs, leading to a host of respiratory issues. It also indirectly contributes to climate change when excess fertilizer inputs to soil are converted into nitrous oxide, a potent greenhouse gas.

In Canada, ammonia emissions have increased by 22 per cent since 1990, and 90 per cent are produced by agriculture, particularly from manures, slurries and fertilizer applications. Mitigating this pollutantwithout limiting fertilizers and food growth for our growing world populationis key to a sustainable future.

>Read more on the Canadian Light Source website

Image: Rachel Hestrin (right) on the beamlines at Canadian Light Source with fellow Cornell researcher Angela Possinger.

Rob Norris joins Canadian Light Source

Former provincial cabinet minister Rob Norris is joining the Canadian Light Source at the University of Saskatchewan, as Senior Government Relations Officer.

“Rob brings a unique depth of experience in our parliamentary system, as well as key policy areas, including innovation, post-secondary education, and industry-related research. I have no doubt he will be of enormous help in strengthening our relationships with government stakeholders at every level, and increasing awareness about the valuable contributions our scientists are making,” said Rob Lamb, CLS Chief Executive Officer.

>Read more on the Canadian Light Source website

Image: CLS CEO Rob Lamb, Environmental & Earth Science Manager Chithra Karunakaran and Senior Government Relations Officer Rob Norris talk on the CLS mezzanine.

Discovery may improve cystic fibrosis treatment

A University of Saskatchewan medical research team has made a groundbreaking finding with potential to lead to more effective, longer-lasting and better-tolerated treatments for cystic fibrosis (CF).

“Though we’re still at an early stage for developing new treatments, this is a major discovery of considerable potential relevance to CF patients,” said Dr. Juan Ianowski (PhD), a physiologist at the USask College of Medicine and senior author of a paper on the finding published today in the online Nature Research journal Scientific Reports.
For over 20 years, doctors have treated CF patients with an inhaled concentrated salt solution called hypertonic saline to increase the volume of airway surface liquid (ASL)—a microscopically thin liquid lining that helps remove infected secretions from the clogged chest of a CF patient. The scientific consensus has been that an osmotic reaction drawing water from the blood was responsible for the beneficial increase in ASL from this saline treatment.
But by using synchrotron imaging at the Canadian Light Source (CLS), the national research facility at USask, the nine-member team has concluded that scientists have not completely understood the body’s reaction to the saline treatment.
>Read more on the Canadian Light Source website

Image: Dr. Julian Tam (MD) and Dr. Juan Ianowski (PhD) are researchers with the university’s Respiratory Research Centre.

Understanding the protein responsible for regulating heartbeats

A new research project uses the Canadian Light Source to help researchers understand the protein responsible for regulating heartbeats. Errors in this crucial protein’s structure can lead to potentially deadly arrhythmias, and understanding its structure should help researchers develop treatments. This protein, calmodulin (CaM), regulates the signals that cause the heart to contract and relax in almost all animals with a heartbeat.

“Usually you find some differences between versions of proteins from one species to another,” explains Filip Van Petegem, a professor in the University of British Columbia’s Department of Biochemistry and Molecular Biology. “For calmodulin that’s not the case—it’s so incredibly conserved.”

It also oversees hundreds of different proteins within the body, adjusting a broad array of cellular functions that are as crucial to our survival and health as a steady heartbeat.

>Read more on the Canadian Light Source website

Image: A surface representation of the disease mutant CaM (D95V, red) in complex with the piece of the voltage-gated calcium channel (blue).

Know your ennemy

Light source identifies a key protein interaction during E. coli infection

Escherichia coli is a common source for contaminated water and food products, causing the condition known as gastroenteritis with symptoms that include diarrhea, vomiting, fever, loss of energy, and dehydration. In fact, for children or individuals with weakened immune systems, this bacterial infection in the gut can be life-threatening.

One of the microbes responsible for gastroenteritis, known formally as enteropathogenic E. coli (EPEC), causes infections by directing a pointed, needle-like projection into the human intestinal tract, releasing toxins that make people sick.

“Enteropathogenic E. coli can fire toxic proteins from inside the bacterium right into the cells of your gut lining,” says Dustin Little, a post-doctoral researcher in the Brian Coombes lab at McMaster University’s Department of Biochemistry and Biomedical Sciences.

>Read more on the Canadian Light Source website

Image: Dustin Little and Brian Coombes in the lab.
Credit: Dustin Little. 

Improving lithium-ion battery capacity

Toward cost-effective solutions for next-generation consumer electronics, electric vehicles and power grids.

The search for a better lithium-ion battery—one that could keep a cell phone working for days, increase the range of electric cars and maximize energy storage on a grid—is an ongoing quest, but a recent study done by Canadian Light Source (CLS) scientists with the National Research Council of Canada (NRC) showed that the answer can be found in chemistry.
“People have tried everything at an engineering level to improve batteries,” said Dr. Yaser Abu-Lebdeh, a senior research officer at the NRC, “but to improve their capacity, you have to play with the chemistry of the materials.”

>Read more on the Canadian Light Source website

Image: The decomposition of a polyvinylidene fluoride (PVDF) binder in a high energy battery.
Credit: Jigang Zhou

New research helps pursuit for malaria vaccine

Scientists from The Hospital for Sick Children (SickKids) identify structure of key malaria protein

Using technology available at the Canadian Light Source synchrotron, SickKids scientists have taken an important step forward on the path to finding effective biomedical interventions to halt the spread of malaria, a disease that affected an estimated 216 million people worldwide in 2016 alone.

Jean-Philippe Julien, a scientist in the Molecular Medicine program at SickKids, and his colleagues focused on a molecule known to be essential for the malaria parasite Plasmodium falciparum to go through the sexual stages of its lifecycle. Disrupting that stage of the lifecycle has the potential to reduce infections and deaths from malaria because parasite transmission between humans would be blocked by inhibiting parasite development in the Anopheles mosquito.

“The protein we looked at was identified several years ago as an important target for malaria parasite biology,” says Julien, who is also a Canada Research Chair in Structural Immunology and an Assistant Professor in the Departments of Biochemistry and Immunology at the University of Toronto. “The field has tried for over a decade to clarify its structure in order to guide the development of biomedical interventions that can curb the spread of malaria.”

>Read more on the Canadian Light Source website

Image: One of the structures of the malaria protein (orange) being recognized by the humanized blocking antibody (green and blue).

First in situ X-ray Absorption study of liquid battery cells

A greener future depends on better batteries: to move away from fossil fuels, we need rechargeable batteries with higher power and energy density to store intermittent energy from solar and wind. Moreover, these batteries could completely replace fossil fuels in vehicles.

Metal-air batteries seem like the answer, with the highest theoretical ability to pack energy into a small space (a property called energy density) of all current battery types.
“If we can achieve the theoretical energy density of metal air batteries and use them in vehicles, we can have much more driving range and make them more competitive with internal combustion engines that are currently used in cars,” says Mohammad Banis, a Western University researcher whose recent work looked at the charge and discharge cycles of a sodium-air battery in action.

Banis, who works in Andy Xueliang Sun’s clean energy research group at Western, spent a full year stationed at the Canadian Light Source to develop new tools for battery research. Observing the real time behaviour of material during charge cycles of a metal air battery presents a puzzle: the soft X-ray technique used typically requires a vacuum chamber, which makes it particularly difficult to study a liquid system.

>Read more on the Canadian Light Source website.

Image: Mohammad Banis at a Canadian Light Source beamline where he studies batteries.

Highly efficient single-atom catalyst could help auto industry

A longer-lasting, higher-efficiency platinum catalyst has been developed by a Dalhousie University-led team, a result with major implications for the automobile industry.

Platinum catalysts help deactivate toxic exhaust gases from traditional car engines. Platinum is also used to help drive the chemical reactions that make zero-emissions hydrogen fuel cells possible – a technology that could transform automobiles as we know them.

The new catalyst combines gold and platinum to form what’s known as a single-atom catalyst, resulting in nearly 100-fold increases in efficiency over market platinum catalysts, says Peng Zhang, the Dalhousie professor who led this research.
Not only is efficiency improved at the outset, but it is maintained through the catalyst’s lifetime: normally, a platinum catalyst works less well over time as carbon monoxide molecules tightly bond to and block platinum from helping reactions along.
Improvements come from two properties: the single atom structure, which maximizes platinum’s active surface area, and the unique electronic properties that adding gold to create an alloy helps to achieve.

>Read more on the Canadian Light Source website

Image: The blue balls represent platinum atoms, surrounded by gold atoms (yellow). This structure maximizes the platinum catalyst’s efficiency.

Innovative educational programs at Canadian Light Source

NSERC PromoScience awards $125K to innovative educational programs at Canadian Light Source.

The Canadian Light Source at the University of Saskatchewan has been awarded $125,000 by NSERC’s PromoScience program, to deliver innovative educational programs expected to reach students in over 100 schools across Canada.
PromoScience funding will enable teachers and students to perform hands-on research addressing real-world issues, through existing and new programs.

A new initiative, the Trans-Canadian Research & Environmental Education (TREE) project, will allow students from even the most remote communities across Canada to participate in a national research program in partnership with the Mistik Askiwin Dendrochronology (MAD) Lab at the University of Saskatchewan, using tree cores to study the environmental history of their community.

In an unprecedented collaboration between research and education, students will gather tree core samples and mail them to the CLS, where scientists will examine their chemical signatures while live streaming with the students who collected each sample. Teaching resources will help students to make sense of the data and to compare with other student samples from across the country, in order to understand how chemical changes in different tree cores correlate to their community’s environmental history.

“Students will learn about the life and nutrient cycles of trees, the trees’ ability to capture information in rings, and the nutrients in soil by working through modules and activities designed to engage students in the areas of STEM and traditional knowledge,” said Tracy Walker, Education Programs Lead at the CLS.

>Read more on the Canadian Light Source website