Pioneering approach advances study of CTCF protein in transcription biology

Scientists at St. Jude collaborated to better understand CTCF. L to R: Beisi Xu, PhD, Chunliang Li, PhD; Judith Hyle; Mohamed Nadhir Djekidel, PhD.
Photo Credit: St. Jude Children's Research Hospital

Scientists at St. Jude Children’s Research Hospital used the auxin-inducible degron 2 system on CTCF, bringing the novel approach to bear on a fundamental protein.

CTCF is a critical protein known to play various roles in key biological processes such as transcription. Scientists at St. Jude Children’s Research Hospital used a next-generation protein degradation technology to study CTCF. Their work revealed the superiority of the approach in addition to providing functional insights into how CTCF regulates transcription. The study, published today in Genome Biology, paves the way for more clear, nuanced studies of CTCF.

Transcription is an essential biological process where DNA is copied into RNA. The process is the first required step in a cell to take the instructions housed in DNA and ultimately translate that code into the amino acid or polypeptide building blocks that become active proteins. Dysregulated transcription plays a role in many types of pediatric cancer. Finding ways to modify or target aspects of the transcriptional machinery is a novel frontier in the search for vulnerabilities that can be exploited therapeutically.

While the biology of CTCF has been extensively studied, how the different domains (parts) of CTCF function in relation to transcription regulation remains unclear.

Mimicking an Enigmatic Property of Circadian Rhythms through an Artificial Chemical Clock

An innovative temperature-compensation mechanism for oscillating chemical reactions based on temperature-responsive gels has been recently reported by researchers at Tokyo Tech. Their experimental findings, alongside a detailed mathematical analysis, hint at the possibility that circadian rhythms found in nature may all rely on a similar mechanism, allowing their period to remain independent of temperature.

Circadian rhythms are natural, internal oscillations that synchronize an organism's behaviors and physiological processes with their environment. These rhythms normally have a period of 24 hours and are regulated by internal chemical clocks that respond to cues from outside the body, such as light.

Although well studied in animals, plants, and bacteria, circadian rhythms all share an enigmatic property—the oscillation period is not significantly affected by temperature, even though the rate of most biochemical reactions changes exponentially with temperature. This clearly indicates that some sort of temperature-compensation mechanism is at play. Interestingly, some scientists have managed to replicate such temperature-invariant qualities in certain oscillating chemical reactions. However, these reactions are often troublesome and require extremely precise adjustments on the reacting chemicals.

Motile Sperm and Frequent Abortions in Spreading Earth moss

The protein PINC has an influence on the motility of sperm cells (left) and the anchoring of spore capsules (right, dark structures) in the moss Physcomitrella. The fluorescence microscope images in the middle show the male sex organ on the left and a young spore capsule on the right. PINC is marked in magenta.
Image Credit: Volker Lüth / University of Freiburg

Freiburg researchers discover that sperm motility and anchoring of the spore capsule in the spreading earth moss Physcomitrella are influenced by the auxin transporter PINC.

As a component of moors, mosses are important for climate conservation. They are also gaining increasing significance in biotechnology and the manufacture of biopharmaceuticals. For the most varied of rationales, mosses are interesting research objects. One reason for this is because they are particularly similar to the first land plants. As a result, they provide insight into the original function of signaling molecules which regulate growth and development in all land plants today. Researchers at the University of Freiburg and the Excellence Cluster CIBSS – Centre for Integrative Biological Signaling Studies – have discovered that transporters of the hormone auxin influence the fertility of spreading earth moss. Their observations have been published in the scientific journal New Phytologist.

Probe can measure both cell stiffness and traction, researchers report

Professor Ning Wang, front right, is joined by researchers, from left, Fazlur Rashid, Kshitij Amar and Parth Bhala.
Photo Credit: Fred Zwicky

Scientists have developed a tiny mechanical probe that can measure the inherent stiffness of cells and tissues as well as the internal forces the cells generate and exert on one another. Their new “magnetic microrobot” is the first such probe to be able to quantify both properties, the researchers report, and will aid in understanding cellular processes associated with development and disease.

They detail their findings in the journal Science Robotics.

“Living cells generate forces through protein interactions, and it’s very hard to measure these forces,” said Ning Wang, a professor of mechanical science and engineering at the University of Illinois Urbana-Champaign who led the research. “Most probes can either measure the forces actively generated by the tissues and cells themselves, a trait we call traction, or they can measure their stiffness – but not both.”

To measure cell stiffness, researchers need a relatively rigid probe that can compress, stretch or twist the tissues and quantify how robustly they resist. But to measure the cells’ own internally generated contractions or expansions, a probe must be relatively soft and supple.

Like other scientists, Wang and his colleagues had already developed probes to measure each of these qualities individually. But he said he wanted to develop a more universal probe that could tackle both at once. Such a probe would allow a better understanding of how these properties influence diseases like arteriosclerosis or cancer, or how an embryo develops, for example.

Wolves eliminate deer on Alaskan Island then quickly shift to eating sea otters

Wolves on an Alaskan island caused a deer population to plummet and switched to primarily eating sea otters in just a few years, a finding scientists at Oregon State University and the Alaska Department of Fish and Game believe is the first case of sea otters becoming the primary food source for a land-based predator.

Using methods such as tracking the wolves with GPS collars and analyzing their scat, the researchers found that in 2015 deer were the primary food of the wolves, representing 75% of their diet, while sea otters comprised 25%. By 2017, wolves transitioned to primarily consuming sea otters (57% of their diet) while the frequency of deer declined to 7%. That pattern held through 2020, the end of the study period.

“Sea otters are this famous predator in the near-shore ecosystem and wolves are one of the most famous apex predators in terrestrial systems,” said Taal Levi, an associate professor at Oregon State. “So, it’s pretty surprising that sea otters have become the most important resource feeding wolves. You have top predators feeding on a top predator.”

Stress may trigger male defense against predators

Photo Credit: Jörgen Wiklund

Only males among the fish species crucian carp have developed a strategy to protect themselves from hungry predators, according to a new study from Lund University in Sweden. The explanation could lie in that the surrounding environment affects the stress system in males and females differently.

Some animals have evolved the ability to swiftly change appearance to defend themselves against predators when necessary - while avoiding the unnecessary costs of that appearance when it is not needed. This is an advantage for animals that live in environments where the risk of being eaten by predators varies. However, there is a difference in the ability of females and males to escape the enemy in this way. Researchers at Lund University have investigated the crucian carp fish species.

“When the smell of predatory fish spreads in the water, the male crucian carp begins to change its appearance, much like a character from Transformers. From having grown in length, the presence of the predatory fish causes the male carp to instead grow in height. The new body shape makes it much more difficult for gape-size limited predators to swallow them. The shape also provides better acceleration, which is an advantage when the fish has to escape from an attacking pike”, explains Jerker Vinterstare, biologist at Lund University.

Genes Common to Different Species Found to Be Connected to the Development of Depression

Affective disorders, also known as mood disorders, are a group of mental illnesses that involve changes in emotional states.
Photo Credit:: Christopher Lemercier

Russian scientists performed a cross-species analysis of brain gene expression in danio fish, rats and humans to identify new common molecular targets for the therapy of affective disorders of the central nervous system induced by chronic stress. The study was able to identify several key brain proteins that may play important roles in the pathogenesis of affective disorders.

The article was published in the journal Scientific Reports. Affective disorders, also known as mood disorders, are a group of mental illnesses that involve changes in emotional states. They include various forms of depression and mania, psychosis, and increased anxiety. They are widespread because they occur not only as independent mental pathologies, but also as complications of neurological and other somatic diseases.

This fact determines the difficulty of diagnosis: people classify low mood, anxiety and irritability as temporary, situational manifestations. According to statistics, emotional disorders of varying severity occur in 20% of people, but only a quarter of them receive qualified help.

Mutant with Counting Disability

Stimulation of the Venus flytrap by touch triggers electrical signals and calcium waves. The calcium signature is decoded; this causes the trap to shut quickly. The DYSC mutant has lost the ability to read and decode the calcium signature correctly.
Image Credit: Ines Kreuzer / Universität Würzburg

The newly discovered dyscalculia mutant of the Venus flytrap has lost its ability to count electrical impulses. Würzburg researchers reveal the cause of the defect.

The carnivorous Venus flytrap (Dionaea muscipula) can count to five: This discovery by Würzburg biophysicist Professor Rainer Hedrich caused worldwide excitement in 2016. How does the plant count? Hedrich's team from Julius-Maximilians-Universität Würzburg (JMU) in Bavaria, Germany, has now described the key component in the journal Current Biology. The researchers found what they were looking for in a mutant of the Venus flytrap that has lost its counting abilities.

Anti-aging gene shown to rewind heart age by 10 years

Centenarian
Photo Credit: Mehmet Turgut Kirkgoz

An anti-aging gene discovered in a population of centenarians has been shown to rewind the heart’s biological age by ten years. The breakthrough, published in Cardiovascular Research and led by scientists at the University of Bristol and the MultiMedica Group in Italy, offers a potential target for patients with heart failure.

Associated with exceptional longevity, carriers of healthy mutant genes, like those living in blue zones of the planet, often live to 100 years or more and remain in good health. These individuals are also less prone to cardiovascular complications. Scientists funded by the British Heart Foundation believe the gene helps to keep their hearts young by protecting them against diseases linked to aging, such as heart failure.

In this new study, researchers demonstrate that one of these healthy mutant genes, previously proved particularly frequent in centenarians, can protect cells collected from patients with heart failure requiring cardiac transplantation.

Avian flu could decimate Australian black swans

Australian black swan
UQ research shows black swans lack some immune genes which help other wild waterfowl combat avian flu.
Photo Credit: Holger Detje

The unique genetics of the Australian black swan leaves the species vulnerable to viral illnesses such as avian flu, University of Queensland research has revealed.

The UQ-led study has generated a first-ever genome of the black swan which revealed the species lacks some immune genes which help other wild waterfowl combat infectious diseases.

Associate Professor Kirsty Short from UQ’s School of Chemistry and Molecular Biosciences said the geographic isolation of Australia’s black swans has meant limited exposure to pathogens commonly found in other parts of the world leading to reduced immune diversity.

“Unlike Mallard ducks for example, black swans are extremely sensitive to highly pathogenic avian influenza – HPAI which is often referred to as bird flu - and can die from it within three days,” Dr Short said.

Stanford Medicine researchers measure thousands of molecules from a single drop of blood

A single drop of blood can yield measurements for thousands of proteins, fats and other biomarkers, researchers at Stanford Medicine found.
Photo Credit: PublicDomainPictures

Researchers at Stanford Medicine have shown they can measure thousands of molecules — some of which are signals of health — from a single drop of blood.

The new approach combines a microsampling device — a tool used to self-administer a finger prick — with “multi-omics” technologies, which simultaneously analyze a vast array of proteins, fats, by-products of metabolism and inflammatory markers.

“Even more importantly, we’ve shown you can collect the blood drop at home and mail it into the lab,” said Michael Snyder, PhD, director of the Center for Genomics and Personalized Medicine and senior author on the research, which was published in Nature Biomedical Engineering on Jan. 19.

Unlike finger-prick testing for diabetes, which measures a single type of molecule (glucose), multi-omics microsampling gives data about thousands of different molecules at once.

The research sounds similar to a well-known approach promoted in the past for testing a single drop of blood, but there are important differences: While the earlier approach was based on replicating existing diagnostic tests, multi-omic microsampling uses a different type of data analysis based on a technology called mass spectrometry, which sorts molecules based on their mass and electronic charge. In addition, the data analysis is performed in a lab, not in a portable box.

Harnessing the healing power within our cells

E. coli bacteria
Photo Credit: Public Domain 

University of Queensland researchers have identified a pathway in cells that could be used to reprogram the body’s immune system to fight back against both chronic inflammatory and infectious diseases.

Dr Kaustav Das Gupta and Professor Matt Sweet from UQ’s Institute for Molecular Bioscience discovered that a molecule derived from glucose in immune cells can both stop bacteria growing and dampen inflammatory responses.

Dr Das Gupta said the finding is a critical step towards future therapeutics that train immune cells.

“The effects of this molecule called ribulose-5-phosphate on bacteria are striking – it can cooperate with other immune factors to stop disease-causing strains of the E. coli bacteria from growing,” Dr Das Gupta said.

“It also reprograms the immune system to switch off destructive inflammation, which contributes to both life-threatening infectious diseases such as sepsis as well as chronic inflammatory diseases like respiratory diseases, chronic liver disease, inflammatory bowel disease, rheumatoid arthritis, heart disease, stroke, diabetes and dementia.”

Cyborg Cells Could Be Tools for Health and Environment

UC Davis biomedical engineers have created semi-living “cyborg cells” that have many of the capabilities of living cells but are unable to divide and grow. The cells could have applications in medicine and environmental cleanup.
Illustration Credit: Cheemeng Tan, UC Davis.

Biomedical engineers at the University of California, Davis, have created semi-living “cyborg cells.” Retaining the capabilities of living cells, but unable to replicate, the cyborg cells could have a wide range of applications, from producing therapeutic drugs to cleaning up pollution. The work was published in Advanced Science.

Synthetic biology aims to engineer cells that can carry out novel functions. There are essentially two approaches in use, said Cheemeng Tan, associate professor of biomedical engineering at UC Davis and senior author on the paper. One is to take a living bacterial cell and remodel its DNA with new genes that give it new functions. The other is to create an artificial cell from scratch, with a synthetic membrane and biomolecules.

The first approach, an engineered living cell, has great flexibility but is also able to reproduce itself, which may not be desirable. A completely artificial cell cannot reproduce but is less complex and only capable of a limited range of tasks.

Old yellow enzyme helps algae against light stress

Biologist Anja Hemschemeier researches green algae.
Photo Credit: RUB, Marquard

Old yellow enzymes have been known for almost 100 years, but their function for organisms is largely in the dark. A Bochum research team publishes initial findings on microalgae.

Old yellow enzymes, or OYEs for short, from the English Old Yellow Enzymes, were discovered in the 1930s and have been heavily researched since then. Because these biocatalysts - colored yellow by an auxiliary molecule - can carry out reactions that are very valuable for the chemical industry, such as pre-medication or fragrance substances. Although OYEs are found in many organisms, their natural role for these living beings is hardly known - possibly because the scientific focus was on biotechnological use. Researchers around private lecturer Dr. Anja Hemschemeier and Prof. Dr. Thomas Happe from the Ruhr University Bochum now shows that an OYE of the unicellular green algae Chlamydomonas reinhardtii is important for the vegetable unicellular organism to protect itself from light stress. The researchers published their results in the journal "Plant Direct" from 15. Published January 2023.

Chloroplast from the father

Tobacco seedlings on growth medium with an antibiotic. Plants with exclusively maternally inherited chloroplasts sensitive to the antibiotic are pale. Two seedlings contain green, intact chloroplasts in the leaves (red arrows). These chloroplasts are resistant to the antibiotic and were passed on from the father plant.
Image Credit: MPI-MP

Under cold conditions, not only the mother plant but also the father plant can pass on its chloroplasts to the offspring

Scientists at the Max Planck Institute of Molecular Plant Physiology in Potsdam (Germany) analyzed for the first time the inheritance of chloroplasts under a wide range of environmental conditions. Contrary to the prevailing view that chloroplasts are only passed on by the mother plant, paternal chloroplasts can also be transmitted to the offspring under cold conditions. Maternal and paternal chloroplasts thus meet in the offspring and may be able to exchange genetic material with each other. The new findings may allow plant breeders for the first time to selectively use traits from the genetic material of chloroplasts.

A story of flowers and bees is the classic introduction to a topic that is still discussed far too scarcely in our society: sex in plants! When plants reproduce, the sperms within the pollen grains fuse with the egg cell within the flower the pollen has landed on. In this way, the genetic material of the cell nuclei of both parents is combined in the seed. This is important, as it allows harmful mutations to be purged that otherwise would accumulate in the genetic material over generations.

Highly accurate test for common respiratory viruses uses DNA as ‘bait’

Doctor examining a patient
Photo Credit: Thirdman

The test uses DNA ‘nanobait’ to detect the most common respiratory viruses – including influenza, rhinovirus, RSV and COVID-19 – at the same time. In comparison, PCR (polymerase chain reaction) tests, while highly specific and highly accurate, can only test for a single virus at a time and take several hours to return a result.

While many common respiratory viruses have similar symptoms, they require different treatments. By testing for multiple viruses at once, the researchers say their test will ensure patients get the right treatment quickly and could also reduce the unwarranted use of antibiotics.

In addition, the tests can be used in any setting, and can be easily modified to detect different bacteria and viruses, including potential new variants of SARS-CoV-2, the virus which causes COVID-19. The results are reported in the journal Nature Nanotechnology.

The winter cold, flu and RSV season has arrived in the northern hemisphere, and healthcare workers must make quick decisions about treatment when patients show up in their hospital or clinic.

Joint study reveals how DNA unzipping machine works, shedding lights on cancer therapy

An initial open structure (IOS) is formed upon binding of human MCM double hexamer (hMCM-DH) to origin DNA.
Illustration Credit: Image modified from original illustration of Li et al, 2023 Cell 186, 1-14. Source/ Hong Kong University of Science and Technology

Scientists from The Hong Kong University of Science and Technology (HKUST), The University of Hong Kong (HKU) and Institut Curie, France have jointly uncovered a new mechanism of the human MCM2-7 complex in regulating replication initiation, which can be used as a novel and effective anticancer strategy with the potential for selective killing of cancer cells. The findings were recently published in the Cell journal.

Human life begins with a single fertilized egg in the mother’s womb. This egg propagates through cell divisions and develops into our multicellular body. During each cell division, our genome DNA, the blueprint of genetic information, is accurately replicated. Each cell carries roughly 2 meters of DNA organized into 23 pairs of chromosomes. In our lifetime (~70 years), our body will synthesize more than a light year’s length of DNA of ~1016 meters - the distance light travels in one year. The replication process requires the DNA duplex to be first melted and then separated into two single-stranded templates for DNA polymerases to synthesize as complement strands. Any misregulation of this process can cause dire consequences, such as tumorigenesis and inherited genetic disorders.

Organelles grow in random bursts

Shankar Mukherji, assistant professor of physics in Arts & Sciences
Photo Credit: Washington University in St. Louis

Eukaryotic cells — the ones that make up most of life as we know it, including all animals, plants and fungi — are highly structured objects.

These cells assemble and maintain their own smaller, internal bits: the membrane-bound organelles like nuclei, which store genetic information, or mitochondria, which produce chemical energy. But much remains to be learned about how they organize themselves into these spatial compartments.

Physicists at Washington University in St. Louis conducted new experiments that show that eukaryotic cells can robustly control average fluctuations in organelle size. By demonstrating that organelle sizes obey a universal scaling relationship that the scientists predict theoretically, their new framework suggests that organelles grow in random bursts from a limiting pool of building blocks.

The study was published Jan. 6 in Physical Review Letters.

“In our work, we suggest that the steps by which organelles are grown — far from being an orderly ‘brick-by-brick’ assembly — occur in stochastic bursts,” said Shankar Mukherji, assistant professor of physics in Arts & Sciences.

Lost in Translation: How "Risky" Amino Acids Abort Elongation in Protein Synthesis

Elongation, a crucial step in the translation process of protein synthesis, gets disrupted by amino acid sequences with an abundance of N-terminal aspartic and glutamic acid residues in eukaryotic cells, discovered researchers from Tokyo Tech and University of Hyogo. The team's findings show that these "risky" amino acids can destabilize the ribosomal machinery. As a consequence, most proteomes tend to avoid incorporating them at the N-terminals of peptide sequences, indicating a bias in amino acid distribution.

Life depends on the precise functioning of several proteins synthesized in cells by ribosomes. This diverse set of proteins, known as a proteome, is maintained by the robust translation elongation of amino acid sequences taking place in the ribosomes. The translation mechanisms which ensure that nascent chains of polypeptides—long chains of amino acids—are elongated without getting detached are conserved in all living organisms. However, the rates of elongation are not constant. Elongation is often interrupted by interactions between positively charged nascent polypeptides and negatively charged ribosomal RNA.

Ludwig Cancer Research study uncovers novel aspect of tumor evolution and potential targets for therapy

 Ping-Chih Ho, Ludwig Lausanne Associate Member
Photo Credit: Ludwig Cancer Research

A Ludwig Cancer Research study has discovered that the immune system’s surveillance of cancer can itself induce metabolic adaptations in the cells of early-stage tumors that simultaneously promote their growth and equip them to suppress lethal immune responses.

Led by Ludwig Lausanne Associate Member Ping-Chih Ho and published in Cell Metabolism, the study details the precise mechanism by which this “immunometabolic editing” of emergent tumors occurs in mouse models of the skin cancer melanoma and identifies a novel biochemical signaling cascade and proteins that orchestrate its effects. Aside from illuminating a previously unknown dimension of tumor evolution, the findings hold significant promise for improving the efficacy of cancer immunotherapy.

“We have uncovered dozens of metabolic enzymes that contribute to immune evasion in melanoma tumors,” said Ho. “These enzymes, as well as some of the individual components of the signaling pathway we’ve identified, represent a rich trove of potential drug targets to undermine the defenses erected by immunometabolic editing. Such drugs could make tumors vulnerable to immune clearance and could also be used in combination with checkpoint blockade and other immunotherapies to overcome the resistance most cancers have to such treatments.”