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Karen de Mesy Bentley is studying how S. aureus bacteria enter tiny channels in bone, where they can elude immune or antibiotic attack, then cause reinfection.

Researchers show how elusive bacteria hide in bone channels

Researchers at the Center for Musculoskeletal Research have conducted the first systematic study defining where and how Staphylococcus aureus, a bacteria that causes life-threatening bone infections, hides in tiny channels within bones, eluding treatment.

“The challenge with bone infections is that they tend to be incurable,” says Edward Schwarz, the Richard and Margaret Burton Distinguished Professor in Orthopaedics and director of the center. “Surgeons take extra margins around infected bone, reconstruct, and the infection comes back. They don’t understand why this infection keeps coming back and neither did we.”

To investigate, Karen de Mesy Bentley,  director of the Electron Microscopy Shared Laboratory and faculty associate in the Department of Pathology and Laboratory Medicine, performed systematic transmission electron microscopy of S. aureus infected mouse femurs and tibias.

Three parallel canaliculi with varying stages of S.aureus infection. Image by Karen de Mesy Bentley.
Three parallel canaliculi with varying stages of S.aureus infection. Image by Karen de Mesy Bentley.

 

It appeared that S. aureus must squeeze from a round to rod shape, never before documented, to fit into channels called canaliculi that are many times smaller in diameter than the bacteria.

Bentley’s images also suggest that S. aureus can “move,” though not in the traditional sense.  Since it lacks the typical appendages of motile bacteria, S. aureus moves by dividing asymmetrically and pushing daughter cells in a desired direction, such as into canaliculi.

Several images showed lone bacteria attaching to canaliculi openings in the absence of any crowding pressure. They also appeared to be dividing abnormally – aligning the plane of division near the opening rather than splitting down the middle, so the daughter cells will be extruded into the channel.

Other evidence led the team to conclude that the bacteria were not getting into the channels by chance or accident, but rather by preference.

“This may explain why surgeons see reinfections, as well as several reports published in medical journals where spontaneous recurrence of infection appears 50-75 years later,” says Bentley.

The team is currently investigating human bone tissue and has preliminary evidence that S. aureus also colonizes canaliculi of patients with S. aureus bone infections.

Read more here.


Study suggests way to target cancer cell metabolism

Cancer cells have their own shrewd metabolism, allowing them to reproduce very quickly. A discovery by two University researchers may provide a way to manipulate cancer-cell metabolism to stop or slow the disease, Lydia Fernandez reports in the latest issue of Dialogue, the Wilmot Cancer Institute magazine.

Cancer cells switch from burning to fermenting sugar, a process that’s fueled by cancer-causing mutations, according to findings by the labs of Joshua Munger,  associate professor of biochemistry and biophysics, and Hucky Land, the Robert and Dorothy Markin Professor and chair of biomedical genetics and director of research at the Wilmot Cancer Institute. The researchers also found that sugar fermentation in cancer cells facilitates the consumption of glutamine, another nutrient source. Glutamine is abundant in the bloodstream, and cancer cells devour it to support cell division.

“Our paper demonstrates that cancer cells, but not normal cells, depend on this link between sugar fermentation and glutamine consumption,” Land says. “This suggests a novel way that we might be able to intervene with treatment.”

Bradley Smith, a staff scientist in the Land lab, led the laboratory experiments conducted with colon cancer cells. Early data show that by blocking enzymes that are specific to colon cancer cell metabolism, tumor growth can be slowed or stopped.  Elsewhere, scientists are studying the metabolism of pancreatic cancer cells and other cancers.

Next, Land says, researchers want to learn whether the metabolism of cancer cells changes and adapts as the disease spreads, and whether different cancers have different metabolic actions.

Read more here.


Brain protein predicts recovery time following concussion

A team led by Jessica Gill of the National Institute of Nursing Research and Jeffrey Bazarian,  professor of emergency medicine, report that elevated levels of the brain protein tau following a sport-related concussion are associated with a longer recovery period and delayed return to play for athletes. The findings, published in Neurology, suggest that tau, which can be measured in the blood, may serve as a marker to help physicians determine an athlete’s readiness to return to the game.

The researchers evaluated changes in tau in 46 Division I and III college athletes who experienced a concussion. Tau — which plays a role in the development of chronic traumatic encephalopathy or CTE, frontotemporal dementia, and Alzheimer’s disease — was measured in preseason blood samples and again within 6 hours following concussion using an ultra-sensitive technology that allows researchers to detect single protein molecules.

“Athletes are typically eager to get back to play as soon as possible and may tell doctors that they’re better even when they’re not,” Bazarian says. “Tau is an unbiased measurement that can’t be gamed; athletes can’t fake it. It may be that tau combined with current clinical assessments could help us make more informed return-to-play decisions and prevent players from going back to a contact sport when their brains are still healing.”

Read more here.


Introducing a new faculty member

Thomas Weber has joined the Department of Earth and Environmental Sciences as an assistant professor after completing a postdoctoral position at the University of Washington’s School of Oceanography. Weber uses numerical models to explore the links among marine ecosystems, elemental cycling, and the global climate system. His doctoral work at University of California, Los Angeles, provided insights into oceanic sources and sinks of fixed nitrogen. In his postdoctoral work he explored the timescales of oceanic carbon storage and transfer of carbon to the deep ocean by sinking organic particles. He is involved in the global GEOTRACES project, which aims to map the distributions of rare elements in the ocean and understand their cycling.


PhD dissertation defenses

Mallory Scott, Biophysics, “Auxiliary α2(delta) Subunits Confer Selectivity of Recombinant CaV2 Channel Subtype Membrane Expression in Rat Sympathetic Ganglia.” 9 a.m., Jan. 13, 2017. Neuman Room (1-6823). Advisor: Paul Kammermeier.

Eva Bodman, Physics and Astronomy, “Modeling Variability and Irregular Transits from Circumstellar Disks and Debris.” 3:30 p.m., Jan. 18, 2017. Bausch and Lomb 372. Advisor: Alice Quillen.

Alina Monteagudo-Caballero, Pharmacology, “Transglutaminase 2 Role in Neurological Disease and Injury: Alterations in Proliferation, Migration, and Metabolism.” 10 a.m., January 19, 2017. K-307 Auditorium (3-6408). Advisor: Gail Johnson.

David Anderson, Electrical Engineering, “Driver-Array Based Flat-Panel Loudspeakers: Theoretical Background and Design Guidelines.” 10 a.m., January 20, 2017. Computer Studies Building Room 426. Advisor: Mark Bocko.

Berkeley Fahrenthold, Neuroscience, “Assessment of the Involvement of Intrinsic and Extrinsic Cell Death Pathways in Retinal Ganglion Cell Death after Excitotoxic Injury.” 10 a.m., January 20, 2017. Whipple Auditorium (2-6424). Advisor: Richard Libby.

Yuan Xue, Materials Science, “A Novel Ion Conductive Gel Polymer Electrolyte for Sodium-air Battery Application.” 1 p.m., January 23, 2017. Hopeman 224. Advisor: John Lambropoulos.

Kelli Fagan, Neuroscience, “The Genetic Sex of the Sensory Neuron ADF Confers Pheromone Attraction in C. elegans.” 1 p.m., January 23, 2017. Ryan Case Method Room (1-9576). Advisor: Douglas Portman.

Wenli Wang, Genetics, “RNA Gain-of-function Mechanism and Biomarker Development for Myotonic Dystrophy Type 1.” 9 a.m., February 1, 2017. Whipple Auditorium (2-6424). Advisor: Charles Thornton.


Mark your calendar

Jan. 31: Deadline to enter “America’s Got Regulatory Science Talent” competition, promoting student interest in the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products. Click here for information and instructions on how to apply.

March 20: Deadline to submit applications for a University Research Award of up to $37,500, matched by the applicant’s home school for a total of $75,000. The program provides seed money on a competitive basis for innovative research projects that are likely to obtain external support.  Completed applications should be directed to adele.coelho@rochester.edu. Click here to view the full RFP.

March 20: Deadline to submit applications for an AS&E PumpPrimer II award. Click here for more information. Faculty in the School of Arts & Science should refer questions to Debra Haring, and those in the Hajim School of Engineering to Cindy Gary.



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