Understanding how motor proteins shape our cells

Understanding the busy networks inside our cells can help researchers develop new cancer treatments and prevent dangerous fungal infections.

With the help of the Canadian Light Source (CLS) at the University of Saskatchewan, a research team led by John Allingham from Queen’s University and Hernando Sosa from the Albert Einstein College of Medicine has shed light on a protein that regulates the intricate microscopic networks that give cells their shape and helps ship important molecules to diverse locations.

Using the CMCF beamline at the CLS and the cryo-EM facility at the Simons Electron Microscopy Center (SEMC) at the New York Structural Biology Center, the team found the missing pieces of an important puzzle.

In their published work, they are the first group to clearly describe the mechanism of action of a tiny motor protein called Kinesin-8 that enables it to control the structures of microtubule fiber networks inside the cell.

Read more on the CLS website

Image: Cells, Canadian Light Source.

X-rays allow us to quickly develop high-strength steels

Knowing how strong a piece of steel is, especially the stainless steel used in everything from cars to buildings, is vitally important for the people who make and use it. This information helps to keep people safe during crashes and to prevent buildings from collapsing.

Accurately predicting the strength of a steel prototype based on its microstructure and composition would be indispensable when designing new types of steel, but it has been nearly impossible to achieve — until now.

“Designing/making the best-strength steel is the hardest task,” said Dr Harishchandra Singh, an adjunct professor at NANOMO and the Centre for Advanced Steels Research at the University of Oulu in Finland.

Estimating the contribution of various factors towards designing high-strength novel steel has traditionally required numerous tests that can take months, according to Singh. Each test also requires a new sample of the prototype. 

Read more on the CLS website

Image: Dr Harishchandra Singh, an adjunct professor at NANOMO and the Centre for Advanced Steels Research at the University of Oulu in Finland. He is standing next to steel components in the spectroscopy lab at NANOMO.

Canadian Light Source’s #My1stLight on the Far Infrared Beamline in 2005

The Queen of England helped us get the beamline operating in May of 2005, while she was visiting Saskatchewan and the Canadian Light Source with Prince Philip. The ring had been operating but the IR beamlines needed vacuum bellows installed due to delays in shipment. These would complete the UHV chambers to the window outside the shield wall. There were no beam outages on the schedule long enough to do this for 6 months into the fall, so the IR operation was being badly delayed.

But! the CLS had to shut down for a day before the Royal visit on Friday May 20*, to allow security screening and preparation for the Royals. So with two days of no-beam, the technicians quickly vented the ring magnet cell and installed the bellows and we had nearly 48 hours to pump down and bake the system. Then on Sat May 21 at 12:30 pm there was beam in the ring (thankfully no leaks from the bellows!) and the search for beam began. The M2 mirror was steered until a spot of light was seen glowing near the edge of the UHV window. This glow was adjusted to line up along one side, and a lateral scan was made while recording a video at the window.

At the controls was Dr. Dominique Appadoo, now at the Australian Synchrotron, who was the Far IR beamline scientist at the time. Assisting were Tim May the optics designer/project manager for the IR beamlines, and Craig Hyett a graduate student working on the IR beamlines. Subsequently the first light was steered out of the window port on the Mid IR beamline.

Image: Tim and Dominique searching for first light

* Read more on the CLS website

Cutting-edge imaging yields new insights into stroke

Synchrotron’s “superhuman vision” made it easy to detect markers of brain damage.

Hemorrhagic stroke, where a weakened vessel in the brain ruptures, can lead to permanent disability or death. Across the globe, over  15 million people are coping with its effects.

A study by researchers from the University of Saskatchewan (USask) and Curtin University in Australia has moved us one step closer to identifying when the bleeding associated with a hemorrhagic stroke starts – critical information for improving patient outcomes.

Time is of the essence when it comes to stroke; the sooner doctors can start treatment, the better the odds they can limit damage.

Using the Mid-IR beamline at the Canadian Light Source at USask, the team examined brain tissue samples with a special technique called Fourier-transform infrared imaging. The researchers were led by Dr. Lissa Peeling, a neurosurgeon at the Royal University Hospital and an Associate Professor in the Department of Surgery at USask.

The novel approach enabled the researchers to identify changes in the brain specific to hemorrhagic stroke.

Dr. Jake Pushie, a member of Dr. Kelly’s and Dr. Peeling’s research team at USask’s College of Medicine, said the combination of the beamline and infrared imaging made it easy to detect markers of brain damage caused by hemorrhagic stroke.

“In a sense, this is giving us ‘superhuman vision’ to look at these brains and map out what’s happening metabolically,” said Pushie.

With synchrotron technology, the team could see where a bleed originated and the extent of oxidative damage it caused – something impossible to do with a microscope or traditional approaches to imaging. Their findings were published in Metallomics.

Armed with this new approach, and a better understanding of what they are looking for, Pushie and colleagues will now go back through their extensive “library” of stroke tissue samples to gain a clearer picture of the speed at which oxidative damage begins to ramp up.

Read more on the CLS website

Image: Team member Nicole Sylvain, with USask’s College of Medicine, in a lab at the CLS

 Understanding how the HIV virus evades immune surveillance

About 36 million people have died from AIDS-related illnesses and approximately 38 million people globally are living with HIV.

Dr. Jonathan Cook, a resident physician specializing in medical microbiology at the University of Toronto, is investigating key proteins on the HIV virus that are crucial to developing an effective vaccine.

“These proteins are so interesting because they are necessary for a virus to infect a human,” said Cook. “By blocking their function, we can avert the kinds of infections that you see routinely.”

He and Adree Khondker in the lab of Prof. Jeffrey E. Lee from the Temerty Faculty of Medicine published a paper in Communications Biology that reveals new information on how the HIV virus interacts with immune systems.

Using the CMFC beamline at the Canadian Light Source at the University of Saskatchewan, the research team analyzed the outer proteins on the HIV virus. They discovered that an area of one protein acts as a decoy — diverting the immune system’s response towards a false target.

This tactic allows the virus to successfully infect human cells and to cause disease.

“The immune system recognizes this sequence on the virus, which is usually a good thing. But, in this situation, the antibodies that the immune system makes don’t protect you from infection,” Cook said.

With the help of the CLS, the researchers confirmed that this decoy area on the HIV protein shapeshifts to entice an ineffective immune response.

Read more on the CLS website

Image: Micrographs of crystals from this project that were diffracted at CLS

X-rays capture ageing process in EV batteries

CLS researcher Toby Bond uses x-rays to help engineer powerful electric vehicle batteries with longer lifetimes. His research, published in The Journal of the Electrochemical Society, shows how the charge/discharge cycles of batteries cause physical damage eventually leading to reduced energy storage. This new work points to a link between cracks that form in the battery material and depletion of vital liquids that carry charge.

Bond uses the BMIT facility at the Canadian Light Source at the University of Saskatchewan to produce detailed CT scans of the inside of batteries. Working with Dr. Jeff Dahn at Dalhousie University, he specializes in batteries for electric vehicles, where the research imperative is to pack in as much energy as possible into a lightweight device.

“A big drawback to packing in more energy is that generally, the more energy you pack in, the faster the battery will degrade,” says Bond.

In lithium-ion batteries, this is because charging physically forces lithium ions between other atoms in the electrode material, pushing them apart. Adding more charge causes more growth in the materials, which shrink back down when the lithium ions leave. Over many cycles of this growing and shrinking, micro-cracks begin to form in the material, slowly reducing its ability to hold a charge.

Read more on the CLS website

Image: Toby Bond adjusts a battery sample on the BMIT beamline

A promising treatment for ovarian cancer

Scientists are looking to harness the immune system to fight cancer

Over 20,000 women across the U.S. and Canada are diagnosed with ovarian cancer annually. The symptoms of this disease are often overlooked until it has spread, making it difficult to detect and treat with conventional methods like radiation and chemotherapy.

Dr. Cory Books, Associate Professor in the Department of Chemistry and Biochemistry at California State University, Fresno, is looking to harness the immune system to fight cancer. He is interested in a particular protein, called mucin, that is found throughout the body and is involved with the production of mucus. This protein is altered in cancer cells, which makes it a unique target for researchers.

“The cell stops adding sugars to the protein, so instead of having this mucus layer, now it has a solid protein layer, and cancer uses that to help spread itself through the body,” Brooks said.

This alteration helps ovarian cancer grow and spread, but it also leaves a signal that can help clinicians locate the cancer and kill it.

“What that means now is that there’s sort of this unique signature that we can target with antibodies to develop a new treatment for cancer,” Brooks said.

Researchers have been interested in this protein since the late 1980s but have never before been able to visualize how antibodies interact with the molecule.

With the help of the CMCF beamline at the Canadian Light Source (CLS) located at the University of Saskatchewan, Brooks and his team were able to see how antibodies bind to the protein for the first time.

Read more on the CLS website

Image: Brandy White, lead author on the study and graduate student with the Department of Chemistry and Biochemistry at California State University, Fresno.

Developing new alloys for hydrogen fuel and catalysis

An alloy is a metal that contains two or three different elements. Steel, for instance, is an alloy of iron and carbon that offers increased strength as a building material.

By mixing more elements together, scientists hope to create new and improved alloys with increased strength and improved corrosion resistance, which could help many industry sectors to reduce costs.

“The trouble is that when you try to make a traditional alloy with more than a couple of elements, the elements tend to separate from each other and clump together,” said David Morris, a PhD student in the Department of Chemistry at the Dalhousie University.

That’s why his research team is interested in alloys with five or more elements that have a highly disordered nature. This chaotic property causes the elements to disperse throughout the mixture and prevent clumping. “You can get alloys with elements that wouldn’t usually go together,” he said.

Morris and his colleagues, including Liangbing Hu’s group from the University of Maryland who synthesized the samples using a special carbothermal shock method, are investigating two alloy samples, one made of five elements and another with fifteen.

“Early experiments suggested that the five-element alloy has high catalytic activity for ammonia decomposition, a process used to make hydrogen fuel, but they potentially have all kinds of applications,” he said.

The team gathered data at the Advanced Photon Source (APS) in Illinois, thanks to the facility’s partnership with the Canadian Light Source (CLS) at the University of Saskatchewan. Using synchrotron light, Morris could analyze each element in their samples separately and spot the differences in the structures of the two alloys.

The researchers discovered that the fifteen-element alloy had some elements that showed oxidation and the length of some of the bonds between them increased. These properties, however, were not found in the five-element alloy, indicating the properties of these special alloys are highly dependent on their compositions.

“Increased oxidation means they are less stable, which could potentially increase the activity for catalysis,” said Morris. “And unusual bond lengths can change the properties and maybe make a more promising catalytic pathway.”

The group’s next step will be to try and link the changes in structure seen in this experiment to the alloys’ catalytic activity. “If we are able to find certain structural properties that are associated with a high catalytic activity, that would allow us to design more effective catalysts in the future,” said Morris.

Read more on the CLS website

Image: APS

Blowing in the wind

Monitoring dust from legacy mine tailings to keep communities safe

Queen’s university researchers have studied dust blown from legacy mine tailings at the Giant Mine in Yellowknife, NWT and determined vital information to inform future remediation efforts.

Using the CLS@APS, the researchers were able to determine the chemical form of arsenic in dust particles sourced from the Giant Mine tailings which intermittently blow into nearby communities.

“The synchrotron is really useful for looking at dust because you have this really tiny micron scale beam that you can focus on individual dust particles and get really good data,” said Queen’s researcher Alex Bailey, who conducted the study as part of her Master’s.

Giant Mine is a decommissioned gold mine located 5 km North of Yellowknife that is currently being remediated. The main concern around this site is the existence of toxic-to-humans arsenic trioxide which was formed as a byproduct of ore processing in the 1950s and 60s. Arsenic trioxide had been previously found in local soils and lake sediments, and there was a concern from local residents that arsenic trioxide may be present in dust generated from surface tailings which intermittently blows into the community. It was important for the wellbeing and peace of mind of nearby community members to understand what dust from these tailings might carry.

By analyzing dust-sized material from the surface of the mine tailings and dust captured from a strategic location using detailed mineralogical analysis, synchrotron, and more conventional techniques, the team was able to identify what forms the arsenic would take and its implications for human health.

Read more on the CLS website

Image: Alex Bailey at the APS synchrotron collecting uXRD and uXRF data for sieved tailings dust samples

Developing pain medication with fewer side effects

Opiates like morphine and codeine provide many patients with relief: from the ache felt after mild surgery to chronic pain experienced by cancer patients. However, this type of medication can cause multiple side effects and can lead to physical dependency with long-term use. Improving pain medication would help millions of people to have a better quality of life.

Dr. Ken Ng, a professor at the University of Windsor and adjunct professor at the University of Calgary (UCalgary), and Sam Carr, a PhD student from UCalgary, have been working with Dr. Peter Facchini’s group at UCalgary to better understand how natural opiates are produced. The team has narrowed their focus on one enzyme in the last stage of opiate assembly, a process that occurs naturally in the poppy plant.

“Imagine this sort of like an assembly line,” Carr said. “There are a lot of different steps in this specific pathway, and each enzyme contributes a different step from the starting product to the finished drug.”

Read more on the Canadian Light Source (CLS) website

Image: Structure of the enzyme studied, a molecule of codeine, and a seed capsule from an opium poppy.

Credit: Sam Carr.

Developing new drugs for superbugs like MRSA

The team is using bright beams at the Canadian Light Source (CLS) at the University of Saskatchewan to image how potential antibiotic-enhancing drugs interact with a molecule vital for building the cell wall of bacteria.

Staphylococcus aureus (the “SA” part of MRSA) has a thick protective cell wall that can make it difficult for some antibiotic drugs to attack it. That wall is an attractive target for drugs. If a therapeutic can weaken or break the wall, then the bacteria will die.

One protein that makes an attractive target for drugs is called UppS. It is involved in assembling part of the lipid scaffold on which the wall is built. Attacking UppS could weaken the wall and make the bacteria more susceptible to existing antibiotics, says Sean Workman, a postdoctoral researcher in the Department of Biology at the University of Regina.

“By slowing down the function of UppS we can make the bacteria more sensitive to other drugs,” he says.

Eric Brown, a professor in the Department of Biochemistry and Biomedical Sciences at McMaster University, went looking for drugs that could target the early steps in the creation of the cell wall and found clomiphene, an already-approved fertility drug that could interfere with UppS. He and his colleagues then used the same techniques to find several new molecules that could do the same thing, two of which – MAC-0547630 and JPD447 – seemed to be worth a closer look.

Read more on the CLS website

Image:UppS protein crystals used to obtain high resolution diffraction data.

Credit: Canadian Light Source

#LightSourceSelfies – Light Source scientists are innovators

Kathryn Janzen is an Associate Scientist and User Experience Coordinator at the Canadian Light Source. During her #LightSourceSelfie, Kathryn reflects on the light source community saying “The contacts between light sources are really important and everyone is very interested in sharing ideas. We’re also really interested in innovating and finding new ways to use the light source and finding new applications for old techniques.”

Protecting our bones after diabetes and hypertension

On November 14, World Diabetes Day aims to raise awareness for the global health threat posed by diabetes, which affects over 460 million people globally, and to promote coordinated efforts to confront diabetes.

People living with type II diabetes and hypertension face an increased risk of bone fractures. An international team of researchers has used the Canadian Light Source (CLS) at the University of Saskatchewan (USask) to identify a potential bone health therapy that could one day alleviate that problem.

The collaboration between the Bone-Muscle Research Center at the University of Texas at Arlington (BMRC-UTA) and the Colleges of Medicine and Kinesiology at USask explored whether hepatocyte growth factor (HGF) could help reduce the fracture risk for people with type II diabetes. Since 50-85 % of diabetic patients live with hypertension, and both conditions are linked to a higher risk of breaks, this population is particularly vulnerable.

Dr. Kamal Awad, research scientist at the BMRC-UTA and first author on the study, said “bones protect our internal organs and allow us to move, thus maintaining a healthy bone is crucial especially for people suffering from diabetes and hypertension”.

This study focused on HGF, which is a naturally occurring molecule that is known to regulate cell growth throughout the body. Awad said it is also “associated with bone regeneration, remodelling, and the balance between osteoblast and osteoclast, but what was unknown is how HGF affects the chemical structure of the bone.”

Natasha Boyes, a PhD candidate specializing in cardiovascular disease in the College of Kinesiology at USask and first co-author, is interested in the whole-body effects of cardiovascular disease, and explained remodelling as a change process bones undergo throughout a person’s life.

“Most people think bone should be hard,” she said, “but hard bone can be very brittle. What you want is bone with the right architecture, and bone is always changing. Any stimulus can cause bone to adjust its structure. For example, if you’re a runner, your bones will change and adapt to better cope with the pounding (biomechanical stress). That’s remodelling.”

To explore how HGF might improve bone health, the researchers did site-specific injections of HGF on diabetic hypertensive rats, then used spectroscopy at the CLS to study the bone chemical structure with a focus on calcium and phosphorous. The team utilized the facility’s specialized SGMVLS-PGM, and SXRMB beamline facilities for this analysis.

Read more on the CLS website

Image: VLS-PGM beamline

Credit: CLS

Understanding how a key antibody targets cancer cells

Immunotherapy can be used as a precise intervention in cancer treatments. Jean-Philippe Julien is a Canada Research Chair in Structural Immunology, a Senior Scientist in the Molecular Medicine Program at The Hospital for Sick Children (SickKids), and an Associate Professor in the Departments of Biochemistry and Immunology at the University of Toronto. Along with colleagues from the U.S., Spain and Canada, he used the Canadian Light Source at the University of Saskatchewan to study how a candidate antibody therapeutic interacts with a surface receptor on cancer cells, which provides important molecular insights for designing improved cancer therapies. He mentioned how the synchrotron is “incredibly important for researchers like myself” and how “we cannot do the research that we do without it.” The team used the CMCF beamline at the CLS and their findings were published in the Journal of Biological Chemistry.Immunotherapy can be used as a precise intervention in cancer treatments. Jean-Philippe Julien is a Canada Research Chair in Structural Immunology, a Senior Scientist in the Molecular Medicine Program at The Hospital for Sick Children (SickKids), and an Associate Professor in the Departments of Biochemistry and Immunology at the University of Toronto. Along with colleagues from the U.S., Spain and Canada, he used the Canadian Light Source at the University of Saskatchewan to study how a candidate antibody therapeutic interacts with a surface receptor on cancer cells, which provides important molecular insights for designing improved cancer therapies. He mentioned how the synchrotron is “incredibly important for researchers like myself” and how “we cannot do the research that we do without it.” The team used the CMCF beamline at the CLS and their findings were published in the Journal of Biological Chemistry.

Learn more on the CLS website

Image: Jean-Philippe Julien

Credit: Canadian Light Source

Scientists tackle indoor air pollution

People on average spend nearly 90% of their time indoors and, especially in the cold winter months in Canada, this statistic can be even higher. With all that time spent indoors, filtering out pollutants from indoor air is very important for the health of Canadians.

Researchers from the College of Engineering at the University of Saskatchewan (USask) have been developing a catalyst for a new type of air purifying technique that would clean air at room temperature.

“Ozone is one of the strongest purifying agents that has been used in the water treatment industry for a long time. In our research, we use ozone and an effective catalyst to purify indoor air from Volatile Organic Compounds or VOCs,” explained PhD student Mehraneh Ghavami.

Ghavami and co-researcher Dr. Jafar Soltan used the HXMA beamline at the Canadian Light Source (CLS) at USask to discover which types of metal catalysts would work best for eliminating pollutants out of the air and recently published their findings.

Their air purifying system uses ozone gas and a catalyst to remove indoor air pollutants and turn them into carbon dioxide and water.

Read more on the Canadian Light Source website

Image: Mehraneh Ghavami using the CLS’ HXMA beamline

Credit: CLS

Using science to make the best chocolate yet

Scientists used synchrotron technology to show a key ingredient can create the ideal chocolate structure and could revolutionize the chocolate industry.

Structure is key when it comes creating the best quality of chocolate. An ideal internal structure will be smooth and continuous, not crumbly, and result in glossy, delicious, melt-in-your-mouth decadence. However, this sweet bliss is not easy to achieve.

Researchers from the University of Guelph had their first look at the detailed structure of dark chocolate using the Canadian Light Source (CLS) at the University of Saskatchewan. Their results were published today in Nature Communications.

“One of the major problems in chocolate making is tempering,” said Alejandro Marangoni, a professor at the University of Guelph and Canada Research Chair in Food, Health and Aging. “Very much like when you temper steel, you have to achieve a certain crystalline structure in the cocoa butter.”

Skilled chocolate makers use specialized tools and training to manipulate cocoa butter for gourmet chocolate. However, Marangoni wondered if adding a special ingredient to chocolate could drive the formation of the correct crystal structure without the complex cooling and mixing procedures typically used by chocolatiers during tempering.

Read more on the Canadian Light Source website

Image: Dr. Saeed Ghazani tempering chocolate. Dept. Food Science University of Guelph.