(Press-News.org)
PORTLAND, Oregon -- New research from Oregon Health & Science University could one day lead to therapies that prevent or treat diseases and infections tied to a protein that’s found in all human cells.
A study published today in the journal Molecular Cell describes how the protein ubiquitin is modified during a bacterial infection. The study details the steps taken to create a form of the protein known as lysine 6 polyubiquitin, where a long chain of ubiquitin molecules are linked through the amino acid lysine. This form of ubiquitin helps cells communicate by sending a molecular message — communication that remains poorly understood.
Previous research has indicated that this form of ubiquitin may be linked to the development of Parkinson’s disease and breast cancer. However, the details of how lysine 6 polyubiquitin is formed or how it is involved in disease aren’t yet clear.
To explore this, OHSU scientists turned their attention to illness-causing bacteria and how they manipulate lysine 6 polyubiquitin during infection. Researchers isolated enzymes used by E. coli and Salmonella to cause food poisoning and other illnesses, and observed how the enzymes interacted with ubiquitin.
The team learned that one particular enzyme was central to building up lysine 6 polyubiquitin.
In earlier, related research that was published in January, the same scientists found that a different enzyme from a different illness-causing bacteria, Legionella pneumophila — which causes a type of pneumonia called Legionnaires’ disease — actively breaks apart the same molecule during infection.
This means different enzymes have different impacts on the same lysine 6 polyubiquitin during infection.
“Knowing how lysine 6 polyubiquitin is regulated is an important first step,” said the study’s senior researcher, Jonathan Pruneda, Ph.D., an assistant professor of molecular microbiology and immunology in the OHSU School of Medicine. “We’ll use this knowledge as a foundation for future research, including exploring how bacteria take advantage of ubiquitin while infecting cells.
“One day, I hope we can harness this research to develop new ways to prevent and treat infections and disease.”
Pruneda and colleagues are currently digging into how the regulation of lysine 6 polyubiquitin is involved in Parkinson’s disease and breast cancer.
REFERENCE: Tyler G. Franklin, Peter S. Brzovic, Jonathan N. Pruneda, Bacterial ligases reveal fundamental principles of polyubiquitin specificity, Molecular Cell, Dec. 12, 2023, https://doi.org/10.1016/j.molcel.2023.11.017.
This research was supported by the National Institutes of Health’s National Institute of General Medicine Sciences (grants 1R35GM144127, P30GM133894 and R35GM142486), U.S. Department of Energy’s Office of Basic Energy Sciences (contract DE-AC02-76SF00515), the U.S. Department of Energy’s Office of Biological and Environmental Research, Oregon Health & Science University and the OHSU Program in Molecular and Cellular Biosciences.
This research is solely the responsibility of its authors and does not necessarily represent the official views of the NIH.
Related OHSU News stories:
OHSU researchers now can predict severity of rare genetic disease in children (9/13/23)
OHSU scientists identify molecule that could help treat Parkinson’s (11/9/22)
OHSU researchers identify promising next-generation cancer treatment (2/10/23)
Other links:
Pruneda Lab (OHSU) END
More than one-eighth of the randomized trials of cancer drugs seeking regulatory approval in China in recent years used inappropriate controls to test the effectiveness and safety of the drugs, according to a new study published December 12th in the open access journal PLOS Medicine by Professor Xiaodong Guan of Peking University, China, and colleagues.
In randomized trials, patients are assigned to either a control arm, in which they receive the current optimal treatment, or an experimental arm, in which they receive the new drug being tested. However, studies have previously ...
MADISON – An interdisciplinary team led by University of Wisconsin–Madison scientists has developed a new technique that could help farmers extract useful nutrients such as ammonia and potassium from livestock manure to efficiently make fertilizer and other useful chemical products. While the strategy still needs to be scaled up beyond a proof-of-concept stage, the group's preliminary analyses show it could offer considerable benefits by cutting water and air pollution while simultaneously creating products that farmers could use or sell.
Manure stinks in part because it contains ammonia, one of the more ...
DENVER/Dec. 12, 2023 – A new article published in the journal Methods in Ecology and Evolution by Morris Animal Foundation-funded researchers describes a simplified method to detect a deadly fungus killing European salamanders. The ability to rapidly find the fungus is significant as the disease, although not detected in the U.S., could impact the millions of amphibians and salamanders annually imported.
The fungal pathogen Batrachochytrium salamandrivorans, or Bsal, threatens salamander diversity. Initially identified in northern Europe, evidence suggests it was introduced from Southeast Asia via the pet trade.
“The impacts of Bsal ...
EMBO launches a new award for laboratory sustainability: The EMBO Lab Sustainability Award will recognize new and significant contributions to the development of sustainable wet and dry labs with a focus on their environmental impact. The award will be presented to an individual representing the initiative or project. Applications can be submitted between 15 January and 15 March 2024.
The award winner will have the opportunity to present their initiative or project at scientific events and publish a commentary in EMBO Reports. In addition, the winning project will be supported with a grant of 10,000 euros. The award is one of ...
ROCHESTER, Minn. — Stem cell-based therapy improved quality of life for patients with advanced heart failure, Mayo Clinic researchers and international collaborators discovered in a late-stage multinational clinical trial. In one of the largest studies of cell intervention after a heart attack, patients reported their daily hardship lessened when stem cells optimized for heart repair supplemented standard of care. This clinical study further documented lower death and hospitalization rates among those treated with cell therapy. This research ...
ABSTRACT: LBA-2
SAN DIEGO ― The targeted therapy combination of ibrutinib and venetoclax significantly improved progression-free survival (PFS) and achieved an overall remission rate in 82% of patients with relapsed/refractory mantle cell lymphoma (MCL), according to researchers at The University of Texas MD Anderson Cancer Center. Results from the Phase III SYMPATICO trial were presented at the 2023 American Society of Hematology (ASH) Annual Meeting.
At a median follow-up of 51.2 months, median PFS was 31.9 months with the combination compared to 22.1 months with ibrutinib plus placebo. PFS benefits were consistent across patient subgroups, including those with blastoid-variant ...
DURHAM, N.C. – Identifying an older patient who is at risk for post-operative cognitive dysfunction might be done in the blink of an eye – literally.
Researchers at Duke Health found that a simple EEG measurement detects a signal of cognitive vulnerability when patients are asked to close, then open their eyes. Conducted prior to surgery, the non-invasive readout of brain waves helps predict which patients are at risk of post-operative confusion and attention problems.
“Roughly half of seemingly normal older adults experience problems with thinking, memory or attention after surgery,” said Leah Acker, M.D., Ph.D., assistant professor in ...
In April 2015, looters sacked an ancient cave burial at a site called Urd Ulaan Uneet high within the Altai Mountains of western Mongolia. When police apprehended the criminals, they uncovered, among other artifacts, an elegantly carved saddle made from several pieces of birch wood.
Now, in a new study, researchers from Mongolia collaborating with University of Colorado Boulder archaeologist William Taylor have described the find. The team’s radiocarbon dating pins the artifact to roughly the 4th Century ...
UNIVERSITY PARK, Pa. — Self-propelled nanoparticles could potentially advance drug delivery and lab-on-a-chip systems — but they are prone to go rogue with random, directionless movements. Now, an international team of researchers has developed an approach to rein in the synthetic particles.
Led by Igor Aronson, the Dorothy Foehr Huck and J. Lloyd Huck Chair Professor of Biomedical Engineering, Chemistry and Mathematics at Penn State, the team redesigned the nanoparticles into a propeller shape to better control their movements and increase their functionality. ...
Karandeep Singh, MD, has been recruited as the Joan and Irwin Jacobs Endowed Chair in Digital Health Innovation at University of California School of Medicine and named as the inaugural chief health artificial intelligence (AI) officer at UC San Diego Health, a newly developed position for the region’s only academic medical center.
This new role will be effective December 29, 2023.
In this position, Singh will focus on implementing change that advances safety and health outcomes in acute and ambulatory settings. His contributions will be pivotal in bringing innovation to ...
