. Scientific Frontline: Biochemistry
Showing posts with label Biochemistry. Show all posts
Showing posts with label Biochemistry. Show all posts

Monday, February 10, 2025

Purdue biochemists discover self-repair function in key photosynthetic protein complex

Sujith Puthiyaveetil and Steve McKenzie look at a plant thylakoid in a lab at the biochemistry building at Purdue University.
Photo Credit: Purdue Agricultural Communications/Joshua Clark

Cyanobacteria began contributing oxygen to Earth’s mostly noxious atmosphere more than 2 billion years ago. The photosystem II protein complex now shared by various lineages of cyanobacteria, algae and land plants has served as a major site of oxygen production throughout the history of life on Earth ever since.

Ironically, receiving too much light can damage photosystem II and erode the photosynthetic efficiency of plants. Purdue University biochemists Steven McKenzie and Sujith Puthiyaveetil have gleaned new, long-hidden details about how photosystem II repairs itself. McKenzie and Puthiyaveetil’s findings have been published in the journal Plant Communications.

“The photosystem II splits water and extracts electrons and protons, leaving oxygen as a by-product. Photosystem II thereby powers life on Earth,” said Puthiyaveetil, associate professor of biochemistry. Even so, “it’s still fairly poorly understood how these huge protein complexes that use light energy to produce oxygen are able to be repaired and maintained so efficiently across different lineages of plants, algae and cyanobacteria.”

Sunday, February 9, 2025

Research Pinpoints Weakness in Lung Cancer’s Defenses

A microscope image of lung cancer cells (purple) containing the activated form of a metabolic enzyme called GUK1 (brown) that supports cancer growth.
Image Credit: Haigis lab

Lung cancer is a particularly challenging form of cancer. It often strikes unexpectedly and aggressively with little warning, and it can shapeshift in unpredictable ways to evade treatment.

While researchers have gleaned important insights into the basic biology of lung cancer, some of the disease’s molecular maneuvers have remained elusive.

Now, a team led by scientists at Harvard Medical School has made strides in understanding how a genetic flaw in some lung cancers alters cancer cell metabolism to fuel the disease.

Working with mouse models and human cancer cells, the researchers identified a metabolic enzyme called GUK1 in lung cancers harboring an alteration in the ALK gene. Their experiments showed that GUK1 plays an important role in boosting metabolism in tumor cells to help them grow.

The findings, reported in Cell and supported in part by federal funding, provide a clearer picture of how metabolism works in lung cancer.

The research could set the stage for developing therapies that target GUK1 to curb cancer growth, the team said.

Friday, February 7, 2025

Discovery of unexpected collagen structure could ‘reshape biomedical research’

Jeffrey Hartgerink is a professor of chemistry and bioengineering at Rice.
Photo Credit: Courtesy of Jeffrey Hartgerink / Rice University

Collagen, the body’s most abundant protein, has long been viewed as a predictable structural component of tissues. However, a new study led by Rice University’s Jeffrey Hartgerink and Tracy Yu, in collaboration with Mark Kreutzberger and Edward Egelman at the University of Virginia (UVA), challenges that notion, revealing an unexpected confirmation in collagen structure that could reshape biomedical research.

The researchers used advanced cryo-electron microscopy (cryo-EM) to determine the atomic structure of a packed collagen assembly that deviates from the traditionally accepted right-handed superhelical twist. Published in ACS Central Science, the study suggests collagen’s structural diversity may be greater than previously believed.

“This work fundamentally changes how we think about collagen,” said Hartgerink, professor of chemistry and bioengineering. “For decades, we have assumed that collagen triple helices always follow a strict structural paradigm. Our findings show that collagen assemblies can adopt a wider range of conformations than previously thought.”

Spliceosome: How Cells Avoid Errors When Manufacturing Mrna

Quality control during splicing: When an error in the precursor mRNA is detected, the spliceosome is blocked, the recruited control factors interrupt the “normal” cycle, and a molecular short circuit causes the spliceosome to disassemble.
Image Credit: © K. Wild, K. Soni, I. Sinning

A complex molecular machine, the spliceosome, ensures that the genetic information from the genome, after being transcribed into mRNA precursors, is correctly assembled into mature mRNA. Splicing is a basic requirement for producing proteins that fulfill an organism’s vital functions. Faulty functioning of a spliceosome can lead to a variety of serious diseases. Researchers at the Heidelberg University Biochemistry Center (BZH) have succeeded for the first time in depicting a faultily “blocked” spliceosome at high resolution and reconstructing how it is recognized and eliminated in the cell. The research was conducted in collaboration with colleagues from the Australian National University.

Saturday, February 1, 2025

New light-tuned chemical tools control processes in living cells

Jun Zhang, Laura Herzog and Yaowen Wu have found a way to control proteins in living cells.
Photo Credit: Shuang Li

A research group at Umeå University has developed new advanced light-controlled tools that enable precise control of proteins in real time in living cells. This groundbreaking research opens doors to new methods for studying complex processes in cells and could pave the way for significant advances in medicine and synthetic biology.

In our experiments, we were able to demonstrate precise control over several processes in the cell

“Cellular processes are complex and constantly change depending on when and where in the cell they occur. Our new chemical tool with light switches will make it easier to control processes in the cell and study how cells function in real time. We can also determine where we make such regulation with a resolution of micrometres within a cell or tissue”, says Yaowen Wu, professor at the Department of Chemistry and SciLifeLab Group leader at Umeå University.

The intricate choreography of what happens in a cell is based on the precise distribution and interaction of proteins over time and space. Controlling protein or gene function is a cornerstone of modern biological research. However, traditional genetic techniques such as CRISPR-Cas9 often operate on a longer time scale, which risks causing cells to adapt. In addition, the techniques lack the spatial and temporal precision required to study highly dynamic cellular processes.

Tuesday, January 28, 2025

Plant-based substitute for fossil fuels developed for plastic foams

Ziqi Yu (Postdoc), Isaac Nartey Oduro (PhD student) and Daniela Gonzalez- Sepulveda (undergraduate RA) are examining lignin-based polyurethane samples.
Photo Credit: Courtesy of Washington State University

An environmentally-friendly preparation of plant material from pine could serve as a substitute for petroleum-based chemicals in polyurethane foams.

The innovation could lead to more environmentally friendly versions of foams used ubiquitously in products such as kitchen sponges, foam cushions, coatings, adhesives, packaging and insulation. The global market for polyurethane totaled more than $75 billion in 2022.

A Washington State University-led research team used an environmentally-friendly preparation of lignin as a substitute for 20% of the fossil fuel-based chemicals in the foam. The bio-based foam was as strong and flexible as typical polyurethane foam. They report on their work in the journal, ACS Sustainable Chemistry and Engineering.

 “It’s quite novel in terms of the material we generate and the process we have,” said Xiao Zhang, corresponding author on the paper and professor in the Gene and Linda Voiland School of Chemical Engineering and Bioengineering. “Our extracted lignin offers a new class of renewable building blocks for the development of bio-based value-added products.”

Saturday, January 25, 2025

Drawing a Line from the Gut Microbiome to Inflammation and Depression

Morganella morganii bacteria on a plate.
Photo Credit: Ajay Kumar Chaurasiya
(CC BY-SA 4.0)

It’s become increasingly clear that the gut microbiome can affect human health, including mental health. Which bacterial species influence the development of disease and how they do so, however, is only just starting to be unraveled.

For instance, some studies have found compelling links between one species of gut bacteria, Morganella morganii, and major depressive disorder. But until now no one could tell whether this bacterium somehow helps drive the disorder, the disorder alters the microbiome, or something else is at play.

Harvard Medical School researchers have now pinpointed a biologic mechanism that strengthens the evidence that M. morganii influences brain health and provides a plausible explanation for how it does so.

The findings, published in the Journal of the American Chemical Society, implicate an inflammation-stimulating molecule and offer a new target that could be useful for diagnosing or treating certain cases of the disorder. They also provide a roadmap for probing how other members of the gut microbiome influence human health and behavior.

“There is a story out there linking the gut microbiome with depression, and this study takes it one step further, toward a real understanding of the molecular mechanisms behind the link,” said senior author Jon Clardy, the Christopher T. Walsh, PhD Professor of Biological Chemistry and Molecular Pharmacology in the Blavatnik Institute at HMS.

Monday, April 8, 2024

First-of-its-kind integrated dataset enables genes-to-ecosystems research

DOE national laboratory scientists led by Oak Ridge National Laboratory have developed the first tree dataset of its kind, bridging molecular information about the poplar tree microbiome to ecosystem-level processes.
Illustration Credit: Andy Sproles/ORNL, U.S. Dept. of Energy

The first-ever dataset bridging molecular information about the poplar tree microbiome to ecosystem-level processes has been released by a team of Department of Energy scientists led by Oak Ridge National Laboratory. The project aims to inform research regarding how natural systems function, their vulnerability to a changing climate, and ultimately how plants might be engineered for better performance as sources of bioenergy and natural carbon storage.

The data, described in Nature Publishing Group’s Scientific Data, provides in-depth information on 27 genetically distinct variants, or genotypes, of Populus trichocarpa, a poplar tree of interest as a bioenergy crop. The genotypes are among those that the ORNL-led Center for Bioenergy Innovation previously included in a genome-wide association study linking genetic variations to the trees’ physical traits. ORNL researchers collected leaf, soil and root samples from poplar fields in two regions of Oregon — one in a wetter area subject to flooding and the other drier and susceptible to drought. 

Details in the newly integrated dataset range from the trees’ genetic makeup and gene expression to the chemistry of the soil environment, analysis of the microbes that live on and around the trees and compounds the plants and microbes produce.

The dataset “is unprecedented in its size and scope,” said ORNL Corporate Fellow Mitchel Doktycz, section head for Bioimaging and Analytics and project co-lead. “It is of value in answering many different scientific questions.” By mining the data with machine learning and statistical approaches, scientists can better understand how the genetic makeup, physical traits and chemical diversity of Populus relate to processes such as cycling of soil nitrogen and carbon, he said. 

Researchers develop better way to make painkiller from trees

Steven Karlen, left, and Vitaliy Tymokhin, scientists with the Great Lakes Bioenergy Research Center, examine a reactor used to convert chemicals in poplar trees into paracetamol, the active ingredient in Tylenol.
Photo Credit: Chelsea Mamott

Scientists at the University of Wisconsin–Madison have developed a cost-effective and environmentally sustainable way to make a popular pain reliever and other valuable products from plants instead of petroleum.

Building on a previously patented method for producing paracetamol – the active ingredient in Tylenol – the discovery promises a greener path to one of the world’s most widely used medicines and other chemicals. More importantly, it could provide new revenue streams to make cellulosic biofuels — derived from non-food plant fibers — cost competitive with fossil fuels, the primary driver of climate change.

“We did the R&D to scale it and make it realizable,” says Steven Karlen, a staff scientist at the Great Lakes Bioenergy Research Center who led the research published recently in the journal ChemSusChem.

Paracetamol, also known as acetaminophen, is one of the most widely used pharmaceuticals, with a global market value of about $130 million a year. Since it was introduced in the early 1900s, the drug has traditionally been made from derivatives of coal tar or petroleum.

Thursday, April 4, 2024

Vaping additives harm a vital membrane in the lungs, according to new Concordia research

Panagiota Taktikakis (left) and Christine DeWolf: “Understanding the impact of vaping additives on lung surfactant is vital, particularly for younger generations who are more influenced by vaping trends.”
Photo Credit: Courtesy of Concordia University

The health risks associated with consumption of tobacco and cannabis products are well-established by now. Much less understood are the risks associated with vaping, particularly flavored products popular with young adults.

It is an increasingly pressing issue: Statistics Canada says one in 10 Canadians aged 20 to 24 and one in 15 aged 15 to 19 reported to have vaped every day in 2022.

Writing in the journal Langmuir, Concordia researchers show how the e-cigarette additive tocopherol — an organic compound better known as vitamin E — and tocopherol acetate can damage the lungs. The study adds to the growing body of literature on what has become known as electronic cigarette or vaping product use–associated lung injury (EVALI).

When heated and inhaled, the compound embeds in the pulmonary surfactant, a nanoscopically thin lipid protein membrane coating the surface of the alveoli that regulates the oxygen-carbon dioxide gas exchange and stabilizes the lungs’ surface tension during breathing.

Saturday, March 30, 2024

Researchers discover molecule that promotes production of cancer cells in triple-negative breast cancer

Hiroshima University researchers found that AIbZIP is highly upregulated in triple negative breast cancer (TNBC). AIbZIP induces hyper proliferation of TNBC cells by promoting the degradation of p27, a negative regulator for cell proliferation.
Illustration Credit: Atsushi Saito/Hiroshima University

A team of researchers from Hiroshima University has discovered a molecule that promotes the production of cancer cells. This molecule may prove to be a potential therapeutic target in the treatment of triple-negative breast cancer, an aggressive form of breast cancer.

Breast cancer is the most common type of cancer, ranking fifth among all cancers in cancer-related deaths. In 2020, there were 2.3 million new cases of breast cancer reported around the globe. In that year, breast cancer caused 685,000 deaths.

Several studies have reported that a molecule called AIbZIP (androgen induced basic leucine zipper) promotes malignant behavior in different cancer types. So, the research team examined the potential role of AIbZIP in malignant tumors. Their computer simulation analysis revealed that AIbZIP was highly expressed in the luminal androgen receptor subtype of triple negative breast cancer, playing a significant role in cell cycle regulation. They identified a novel mechanism by which AIbZIP regulates cancer cell proliferation in this type of breast cancer.

“We found that AIbZIP is highly upregulated in triple negative breast cancer. AIbZIP plays a crucial role for hyper proliferation of triple negative breast cancer cells by promoting the degradation of p27, a negative regulator for cell proliferation. Our study indicates that AIbZIP may be potential therapeutic target of triple negative breast cancer” said Atsushi Saito, an associate professor and Kazunori Imaizumi, a professor in the Department of Biochemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University.  

Friday, March 22, 2024

Decoding the plant world’s complex biochemical communication networks

PhD candidate Shannon Stirling in Natalia Dudareva’s Lab, transfers DNA into a petunia by using a syringe to inject bacterium into the stigma to activate targeted genes, then isolating the resulting proteins.
Photo Credit: Purdue Agricultural Communications / Tom Campbell

A Purdue University-led research team has begun translating the complex molecular language of petunias. Their grammar and vocabulary are well hidden, however, within the countless proteins and other compounds that fill floral cells.

Being rooted to the ground, plants can’t run away from insects, pathogens or other threats to their survival. But plant scientists have long known that they do send warnings to each other via scent chemicals called volatile organic compounds.

“They use volatiles because they can’t talk,” said Natalia Dudareva, Distinguished Professor of Biochemistry and Horticulture and Landscape Architecture at Purdue. “Plants inform neighboring plants about pathogen attacks. It looks almost like immunization. Under normal conditions, you don’t see any changes in the receiver plant. But as soon as a receiver plant is infected, it responds much faster. It’s prepared for response.”

Plant scientists have long known about this immunization-like priming, but until a few years ago, they had no way to study the process. They needed a marker showing that the plants had detected the volatile compounds.

Dudareva and 13 co-authors describe new details of the detection process in the March 22, 2024, issue of the journal Science. The team includes researchers from Purdue; Université Jean Monnet Saint-Etienne in France; and the University of California, Davis.

Wednesday, March 20, 2024

Natural recycling at the origin of life

Volcanic freshwater lakes, similar to those found in Iceland today, offered a favorable niche on an early earth. The low-salt, alkaline conditions enabled early RNA replication.
Photo Credit: © Dieter Braun

How was complex life able to develop on the inhospitable early Earth? At the beginning there must have been ribonucleic acid (RNA) to carry the first genetic information. To build up complexity in their sequences, these biomolecules need to release water. On the early Earth, which was largely covered in seawater, that was not so easy to do. In a paper recently published in the Journal of the American Chemical Society (JACS), researchers from the team of LMU professor Dieter Braun have shown that in RNA’s struggle with the surrounding water, its natural recycling capabilities and the right ambient conditions could have been decisive.

“The building blocks of RNA release a water molecule for every bond they form in a growing RNA chain,” explains Braun, spokesperson for the Collaborative Research Centre (CRC) Molecular Evolution in Prebiotic Environments and coordinator at the ORIGINS Excellence Cluster. “When, conversely, water is added to an RNA molecule, the RNA building blocks are fed back into the prebiotic pool.” This turnover of water works particularly well under low saline conditions with high pH levels. “Our experiments indicate that life could emerge from a very small set of molecules, under conditions such as those prevailing on volcanic islands on the early Earth,” says Adriana Serrão, lead author of the study.

Study reveals how pH affects the ability of ulcer bacteria to attach

Anna Åberg and Anna Arnqvist Björklund.
Photo Credit: Mattias Pettersson

A study by Anna Arnqvist's research group at Umeå University reveals molecular details about the gastric pathogen Helicobacter pylori's ability to bind to an inflamed stomach and how this is controlled by the stomach's pH. Increased understanding of how H. pylori bacteria can cause a persistent lifelong infection is an important piece of the puzzle in order to ultimately identify the characteristics that contribute to disease.

When the stomach becomes infected with the gastric pathogen Helicobacter pylori, the infection lasts for life if it is left untreated. The infection can cause peptic ulcer disease as well as stomach cancer. The environment within the stomach undergoes continuous changes, requiring the bacteria to adapt by adjusting the expression of certain proteins based on the prevailing conditions.

It is commonly assumed that the stomach has a low pH. However, the pH levels vary significantly, ranging from the highly acidic environment in the stomach lumen to largely neutral conditions at the outermost layer of the stomach epithelial cells, which is protected by a mucus layer. It is in the mucus layer or tightly attached to the outermost cell layer that most H. pylori bacteria are found. The expression of many genes is regulated in response to pH, causing the bacterium to produce varying amounts of proteins depending on the pH of its surroundings.

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