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Biochemistry Research

Unlocking the Complexity of Gene Regulation: New Insights into Transcription Factor Interactions

Research into transcription factors deepen understanding of the ‘language’ of the genome, offering insights into human development.

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New research has significantly advanced our understanding of human gene regulation by identifying specific sequences of proteins called transcription factors that bind to DNA and regulate gene expression. The study, published in Nature, reveals new patterns and preferences in how certain transcription factors interact with each other.

The researchers from the Wellcome Sanger Institute, the University of Cambridge, and their collaborators analyzed 58,000 pairs of transcription factors from human cells using novel algorithms. This analysis allowed them to identify specific sequences that influence gene expression, known as motifs.

These findings have implications for understanding how genes are expressed during embryonic development and how they contribute to disease risk. The researchers’ results reveal new patterns and preferences in how certain transcription factors interact with each other, adding significantly to our understanding of the regulatory code.

The study also has implications for computational models that predict protein structures. While these tools can predict overall structure, they often cannot account for smaller details like transcription factor interactions on DNA. These small interactions have a significant impact on human development but are challenging to predict using current models.

This research marks an important step forward in studying the language of gene expression, particularly in non-coding regions of the genome. These regions, which make up 99% of the genome, do not code for proteins but still play a crucial role in regulating gene expression and disease risk.

Dr. Ilya Sokolov, an author of the study at the Wellcome Sanger Institute, said: “By gaining a deeper understanding of how transcription factors interact when guided by DNA, we hope our research will shed light on the molecular basis of the regulatory code, particularly in the context of developmental disorders.”

Professor Jussi Taipale, senior author of the study and Group Leader at the Wellcome Sanger Institute, said: “The human genome’s regulatory code is very complex, far more complex than the genetic code. Our research into transcription factor interactions unlocks deeper insights into the ‘language’ of the genome.”

Biochemistry Research

Tracking Antibiotic Resistance: A Breakthrough in Computational Tool Development

A research team has developed a computational tool, Argo, designed to accurately track ARGs in environmental samples, providing insights into their dissemination and associated risks.

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The proliferation of antibiotic resistance genes (ARGs) poses a significant threat to public health worldwide. To combat this issue, understanding how ARGs are transmitted and implemented preventive measures is crucial. A research team led by Professor Tong Zhang from the University of Hong Kong has developed an innovative computational tool called Argo that tracks ARGs in environmental samples, providing valuable insights into their dissemination.

The current high-throughput DNA sequencing technique used for tracking ARGs often fails to provide information on the hosts carrying these genes. This limits our ability to accurately assess the risks associated with ARGs and trace their transmission, hindering our understanding of their impact on human health and the environment.

Argo utilizes long-read sequencing, a method that generates significantly longer DNA fragments than traditional short-read sequencing techniques. By assigning taxonomic labels to read clusters (collections of reads that overlap each other), Argo enhances the detection resolution of ARGs. The key difference between Argo and existing tools lies in its method of grouping and analyzing DNA fragments based on their overlaps, rather than individual reads.

The accuracy of host identification is a significant advantage of Argo over existing tools. By solving a “puzzle” using shared features among DNA fragment pieces, researchers can group and label overlapping or similar pieces more effectively. Simulations have shown that Argo achieves the lowest misclassification rate compared to other tools.

While long-read sequencing remains costly for achieving high throughput, the team believes this new method is vital in addressing the growing threat posed by ARGs. Professor Zhang concludes that “Argo has the potential to standardize ARGs surveillance and enhance our ability to trace the origins and dissemination pathways of ARGs, contributing to efforts to tackle the global health threat of antimicrobial resistance (AMR).”

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Biochemistry Research

Unlocking the Secrets of Brown Algae: A Breakthrough in Biotech Applications

Every year, thousands of tons of brown algae are extracted from the seabed to obtain compounds such as alginates, a polymer composed of sugars that has high density and strength, offering potential biotechnological applications. An international team has deciphered the mechanism by which a type of enzyme, called alginate lyase (AL), is capable of degrading these marine biomaterials, allowing them to be used as carriers of drugs, additives or thickeners, among others. These results will help in the development and design of new ‘tailored alginates’ for specific applications, especially in the food and biomedical industries.

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The world of marine biomaterials has long been a treasure trove for scientists seeking innovative solutions. Every year, thousands of tonnes of brown algae are harvested from the seabed, yielding valuable compounds such as alginates, which have potential biotechnological applications. A recent study led by the University of Barcelona has made a groundbreaking discovery in deciphering the mechanism behind alginate lyase (AL), an enzyme capable of degrading these marine biomaterials.

The research team, comprising José Pablo Rivas-Fernández and Carme Rovira from the UB’s Faculty of Chemistry and the UB Institute of Theoretical and Computational Chemistry (IQTCUB), in coordination with Casper Wilkens from the Technical University of Denmark, has published their findings in Nature Communications. This study will significantly contribute to the development and design of new “tailored alginates” for specific applications, particularly in the food and biomedical industries.

Despite the abundance of alginates in the marine environment, their range of opportunities is limited by their inhomogeneous composition. The knowledge of the mechanism of action of AL enzymes when they break down the bonds connecting mannuronic acid-type sugars will help overcome these limitations. “The results lay the groundwork for manipulating these enzymes and designing variants with better catalytic properties and higher efficiency on a large scale,” the researchers explain.

Using industrial techniques and bioprocesses, it will be possible to optimize the production of ‘tailored alginates’ in sufficient quantities to meet society’s needs. This breakthrough also allows for a “better use of natural resources and boost the green economy by using enzymes as key tools in the production of these alginates,” say the authors.

The study was based on computational analysis with the MareNostrum 5 supercomputer, which reconciled previous scientific discrepancies about the number of stages in which the reaction occurs. The simulations have confirmed that the degradation of alginates happens in a single stage and that the polymer breaks at the centre, not at one end. They have also cleared the nature of the transition state as a highly negatively charged species.

This finding suggests that we may be able to control at what point the polymer breaks down by mutations of certain amino acids in the enzyme’s active centre. The enzymes analysed belong to family 7 of lyases, which is the most abundant known to date, allowing extrapolation of the mechanism described to other enzymes with high biotechnological potential.

The results improve understanding of the chemical evolution of alginate during its degradation, a fundamental element for the design of probes capable of identifying and isolating alginate lyases. In this sense, UB researchers are currently working on the design of probes that allow efficient identification of new enzymes active in carbohydrates.

This study is part of Carbocentre, a project funded by a Synergy Grant from the European Research Council (ERC), aiming to advance our understanding of the biotechnological potential of marine biomaterials.

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Biochemistry Research

A Game-Changing Device for TB Diagnoses: Revolutionizing Healthcare for Children

This handheld device is the first that can detect tuberculosis in saliva, in addition to blood and sputum samples, an important breakthrough for testing children and HIV patients, who struggle to produce sputum. The device was found to deliver rapid, accurate results in under an hour, offering a cost-effective and accessible solution for diagnosing TB in resource-limited areas.

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The development of a handheld diagnostic device that can deliver rapid and accurate tuberculosis (TB) diagnoses in under an hour has been hailed as a breakthrough by Tulane University researchers. The smartphone-sized lab-in-tube assay (LIT) provides a cost-effective tool that can improve TB diagnoses, particularly in resource-limited rural areas where healthcare facilities and lab equipment are less accessible.

Over 90% of new TB cases occur in low- and middle-income countries, making it essential to develop innovative diagnostic tools. The LIT device is the first to detect Mycobacterium tuberculosis (Mtb) DNA in saliva, blood, and sputum samples. Saliva is easier to obtain than blood or sputum, and the ability to non-invasively collect accurate results is crucial for successfully testing children.

More than 1 million children fall ill with TB each year, with over half going undiagnosed or unreported, according to the World Health Organization. The current resurgence of TB cases has highlighted the urgent need for effective and accessible diagnostic tools.

The LIT device offers a low-cost solution, costing less than $800 per device and less than $3 per test, in contrast to other commonly used TB testing devices that cost at least $19,000 and around $100 per test. In a study published in Science Translational Medicine, the LIT device demonstrated high accuracy in testing blood samples from children in the Dominican Republic, outperforming another more expensive machine.

“This system reduces the expertise and equipment required for TB diagnosis, which is essential for point-of-care application,” said lead author Brady Youngquist. “Saliva-based testing for TB is particularly exciting because it can be easily obtained in all patients and can be used for portable testing without the need for blood draw.”

The ability to monitor TB treatment progress using blood serum-based testing is also a significant advantage, especially in children and patients living with HIV who often cannot produce sputum. The LIT assay results suggest that blood samples could be used to track treatment progress, closely aligning with patient symptoms.

As the world’s deadliest infectious disease infects an estimated 10 million people a year, it is crucial to develop effective diagnostic tools like the LIT device. With its potential to revolutionize healthcare for children and underserved communities, this breakthrough technology is a significant step towards preventing further spread of TB and saving lives worldwide.

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