TL;DR
- Researchers have recently identified a DNA region known as VNTR2–1 that appears to drive the activity of the telomerase gene, which has been shown to prevent aging in certain types of cells. Knowing how the telomerase gene is regulated and activated and why it is only active in certain cell types could someday be the key to understanding how humans age and how to stop the spread of cancer.
- A new study provides foundational information about SARS-CoV-2’s spike protein.
- Research reveals key differences between single- and double-stranded RNA, insights that may prove useful to fields from agriculture to medicine.
- A bird’s-eye view may take on new meaning thanks to new research. Scientists found that a protein in bird’s retinas is sensitive to the Earth’s magnetic field thus guiding its migratory patterns. That finding could be key to Army navigation of both autonomous and manned vehicles where GPS is unavailable.
- New research has uncovered an essential mechanism coordinating the processes of cell division and adhesion within humans. This discovery has profound potential for advancing understanding of cell adhesion signalling in cancerous tumor progression and metastasis.
- A new study uncovers a near-universal mechanism behind inflammatory memory phenomenon.
- New research finds that sexual reproduction and multicellularity drive diversity among different species.
- Minuscule tunnels through the cell membrane help cells to perceive and respond to mechanical forces, such as pressure or touch. A new study directly investigates what PIEZO channels are doing in the tip-growing cells in moss and pollen tubes of flowering plants, and how.
- New research has found that two types of weevils, common yet invasive beetles in many parts of the world, have been using epigenetic changes to adapt and respond to different toxins in the plants they eat. The findings have implications for how we consider asexual invaders and how successful they can be because of gene regulation.
- A research team has directly reprogrammed whale somatic cells to neuronal cells, and conducted a neurotoxicity test using these cells. Exposure to a metabolite of polychlorinated biphenyls, ubiquitous environmental pollutants, caused apoptosis in the reprogrammed neurons. Transcriptome analysis of 4’OH-CB72-treated whale neurons showed altered expressions of genes associated with oxidative phosphorylation, chromatin degradation, axonal transport, and neurodegenerative diseases.
- And more!
Overview
Genetic technology is defined as the term which includes a range of activities concerned with the understanding of gene expression, advantages of natural genetic variation, modifying genes and transferring genes to new hosts. Genes are found in all living organisms and are transferred from one generation to the next. Gene technology encompasses several techniques including marker-assisted breeding, RNAi and genetic modification. Only some gene technologies produce genetically modified organisms.
Modern genetic technologies like genome editing would not be possible without all the previous generations of genetic technologies that have enabled scientists to discover what genes are, what they do and how DNA can be modified to add, remove or replace genes. You can find major genetic technologies development milestones via the link.
Gene Technology Market
- The valuation of the genetic engineering market is projected to escalate to USD 6.90 MN by the end of 2027.
- Global Genetic Engineering Market is projected to grow at 12.48% CAGR during the assessment period (2017–2027).
- North America holds the largest share in the global genetic engineering market, followed by Europe and the Asia Pacific, respectively.
- Another research provider, MarketsandMarkets, forecasts the genome editing, genome engineering market to grow from USD 3.19 billion in 2017 to USD 6.28 billion by 2022, at a compounded annual growth rate (CAGR) of 14.5% during the forecast period. The key factors propelling market growth are rising government funding and growth in the number of genomics projects, high prevalence of infectious diseases (like COVID-19) and cancer, technological advancements, increasing production of genetically modified (GM) crops, and growing application areas of genomics.
Latest News & Research
Polymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene
by Tao Xu, De Cheng, Yuanjun Zhao, Jinglong Zhang, Xiaolu Zhu, Fan Zhang, Gang Chen, Yang Wang, Xiufeng Yan, Gavin P. Robertson, Shobhan Gaddameedhi, Philip Lazarus, Shuwen Wang, Jiyue Zhu in Proceedings of the National Academy of Sciences
The human body is essentially made up of trillions of living cells. It ages as its cells age, which happens when those cells eventually stop replicating and dividing. Scientists have long known that genes influence how cells age and how long humans live, but how that works exactly remains unclear. Findings from a new study led by researchers at Washington State University have solved a small piece of that puzzle, bringing scientists one step closer to solving the mystery of aging.
A research team headed by Jiyue Zhu, a professor in the College of Pharmacy and Pharmaceutical Sciences, recently identified a DNA region known as VNTR2–1 that appears to drive the activity of the telomerase gene, which has been shown to prevent aging in certain types of cells.
The telomerase gene controls the activity of the telomerase enzyme, which helps produce telomeres, the caps at the end of each strand of DNA that protect the chromosomes within our cells. In normal cells, the length of telomeres gets a little bit shorter every time cells duplicate their DNA before they divide. When telomeres get too short, cells can no longer reproduce, causing them to age and die. However, in certain cell types — including reproductive cells and cancer cells — the activity of the telomerase gene ensures that telomeres are reset to the same length when DNA is copied. This is essentially what restarts the aging clock in new offspring but is also the reason why cancer cells can continue to multiply and form tumors.
Knowing how the telomerase gene is regulated and activated and why it is only active in certain types of cells could someday be the key to understanding how humans age, as well as how to stop the spread of cancer. That is why Zhu has focused the past 20 years of his career as a scientist solely on the study of this gene.
Zhu said that his team’s latest finding that VNTR2–1 helps to drive the activity of the telomerase gene is especially notable because of the type of DNA sequence it represents.
“Almost 50% of our genome consists of repetitive DNA that does not code for protein,” Zhu said. “These DNA sequences tend to be considered as ‘junk DNA’ or dark matters in our genome, and they are difficult to study. Our study describes that one of those units actually has a function in that it enhances the activity of the telomerase gene.”
Their finding is based on a series of experiments that found that deleting the DNA sequence from cancer cells — both in a human cell line and in mice — caused telomeres to shorten, cells to age, and tumors to stop growing. Subsequently, they conducted a study that looked at the length of the sequence in DNA samples taken from Caucasian and African American centenarians and control participants in the Georgia Centenarian Study, a study that followed a group of people aged 100 or above between 1988 and 2008. The researchers found that the length of the sequence ranged from as short as 53 repeats — or copies — of the DNA to as long as 160 repeats.
“It varies a lot, and our study actually shows that the telomerase gene is more active in people with a longer sequence,” Zhu said.
Since very short sequences were found only in African American participants, they looked more closely at that group and found that there were relatively few centenarians with a short VNTR2–1 sequence as compared to control participants. However, Zhu said it was worth noting that having a shorter sequence does not necessarily mean your lifespan will be shorter, because it means the telomerase gene is less active and your telomere length may be shorter, which could make you less likely to develop cancer.
“Our findings are telling us that this VNTR2–1 sequence contributes to the genetic diversity of how we age and how we get cancer,” Zhu said. “We know that oncogenes — or cancer genes — and tumor suppressor genes don’t account for all the reasons why we get cancer. Our research shows that the picture is a lot more complicated than a mutation of an oncogene and makes a strong case for expanding our research to look more closely at this so-called junk DNA.”
Zhu noted that since African Americans have been in the United States for generations, many of them have Caucasian ancestors from whom they may have inherited some of this sequence. So as a next step, he and his team hope to be able to study the sequence in an African population.
Effect of clinical isolate or cleavage site mutations in the SARS-CoV-2 spike protein on protein stability, cleavage, and cell–cell fusion
by Chelsea T. Barrett, Hadley E. Neal, Kearstin Edmonds, Carole L. Moncman, Rachel Thompson, Jean M. Branttie, Kerri Beth Boggs, Cheng-Yu Wu, Daisy W. Leung, Rebecca E. Dutch in Journal of Biological Chemistry
A new University of Kentucky College of Medicine study provides foundational information about SARS-CoV-2’s spike protein.
The spike protein is found on the surface of SARS-CoV-2, the virus that causes COVID-19, and is responsible for its entry into host cells. Because of this function, it is the focus of most COVID-19 vaccines including the Pfizer/BioNTech and Moderna mRNA vaccines.
“The spike protein represents one of the most important therapeutic targets for COVID-19,” said study lead Becky Dutch, vice dean for research in the College of Medicine and chair of the Department of Molecular and Cellular Biochemistry. “This study gives scientists a more comprehensive understanding of how the protein works, which is significant to the continued development of vaccines and therapeutics.”
Dutch’s study provides insight into how stable the spike protein is, how it promotes cell-to-cell fusion and how it is modified. Her team examined the effect of mutations in clinical isolates of the virus on protein stability and function. They also observed spike protein synthesis and processing in bat cells to understand if any differences were observed.
The study found that the majority of the spike protein degrades within 24 hours, which provides more understanding about the process of infection and vaccination. Since mRNA vaccines work by giving instructions to our cells to make the spike protein, this finding gives insight into how long the newly made protein will be present.
Dutch’s team also examined the role of key host factors in cell-to-cell fusion. In addition to binding the virus to target cells, the spike protein can cause fusion between the cell it is made in and a neighboring cell, an effect seen in the lungs of COVID-19 patients.
Dutch says there has been relatively little research done on the spike protein’s cell-to-cell fusion or stability, so the study will contribute to giving researchers a full picture of how the proteins are made and how they function.
Duplex Structure of Double-Stranded RNA Provides Stability against Hydrolysis Relative to Single-Stranded RNA
by Ke Zhang, Joseph Hodge, Anamika Chatterjee, Tae Seok Moon, Kimberly M. Parker in Environmental Science & Technology
Messenger RNA, or mRNA, has been in the news recently as a crucial component of the Pfizer-BioNTech and Moderna COVID-19 vaccines. The nucleic acid looks, for all intents and purposes, like a strand of DNA that has been sliced the long way. It’s what’s known as single-stranded RNA (ssRNA), and it can be found throughout the natural world.
Less common in nature is double-stranded RNA (dsRNA), which has two strands and resembles the well-known DNA double helix. It’s found in some viruses, but for the past few decades, people have been developing synthetic dsRNA for a range of purposes.
Despite our growing familiarity with its potential applications, researchers knew little about a key feature of dsRNA, namely how dsRNA degrades — a particularly important question as one of its most promising applications is in agriculture as a type of pesticide.
Research from the lab of Kimberly Parker, assistant professor of energy, environmental and chemical engineering at the McKelvey School of Engineering at Washington University in St. Louis, has upended common assumptions about the chemical stability of dsRNA that may prove useful to fields from agriculture to medicine. The lab’s findings even may have implications for our understanding of the origins of life.
“Fundamentally, we are challenging a pervasive assumption that what we know about ssRNA behavior predicts dsRNA behavior,” Parker said.
“The general knowledge is that RNA is less stable than DNA,” Parker said. That’s because the RNA structure has a few extra atoms that causes the nucleic acid to degrade by itself to smaller pieces.
But that’s the comparison of ssRNA with DNA. What about the difference between ssRNA and dsRNA?
Parker and first author Ke Zhang, a PhD student in Parker’s lab, set out to investigate dsRNA degradation. The team found that, even though dsRNA has the same basic structure as ssRNA, it was substantially more chemically stable than ssRNA. Even at extremely harsh alkaline pH conditions that caused ssRNA to degrade in minutes, dsRNA persisted. It’s fundamental science, but it also has real consequences.
Although little was known about the processes that break down dsRNA, it has been treated as if it behaves the same as ssRNA not only by researchers, but also by institutions such as the Environmental Protection Agency, which regulates pesticide use.
Recently, dsRNA has become a hot topic in the world of pesticides. The first crops genetically engineered to contain a dsRNA pesticide might be planted as soon as 2022.
“When we look at the environmental fate of dsRNA pesticides, a key question is, ‘Will these things stick around, or are they going to degrade quickly?’” Parker said.
If chemical processes acting on dsRNA cause the structure to break down quickly, “it can be considered potentially safe and you don’t have to worry about it as much,” Parker said. “But if you need more specific conditions for it to break down, particular enzymes for instance, that changes how you have to think about its safety and potential risk to the environment. You can’t rely on chemical instability alone to limit persistence.”
The researchers also investigated how the surprising chemical stability of dsRNA might be harnessed for good. Although dsRNA is chemically stable, it still can be degraded by enzymes that occur everywhere in the environment — and even our bodies. This can make it difficult to store dsRNA pesticides and products, as well as challenging to measure levels of dsRNA accurately because the dsRNA can degrade after the sample is collected but before it is analyzed.
To see if the unique chemical stability of dsRNA could be used to stabilize dsRNA in samples, Zhang looked at how ssRNA and dsRNA degraded in human saliva and soils, each of which has enzymes that work to break down both types of RNA.
“In each case, both types of RNA were degraded quickly by the enzymes in human saliva and soils,” Zhang said. But when the pH was raised to an alkaline state — which would destroy the enzymes, “things were different; we observed ssRNA was also rapidly degraded by the alkaline conditions. However, dsRNA was actually more stable at the higher pH.”
The finding suggests that dsRNA — whether used in pesticides, for medical use or research — should be stored in a high pH environment to confer an extra level of protection.
“Say you work with dsRNA,” Parker said. Maybe you sneeze? “You don’t want to worry about contaminating your samples with saliva. You can raise the pH of your samples of dsRNA, shut down the enzyme degradation, but also avoid having the chemical degradation process.”
The potential to put this knowledge into action goes far beyond pesticides.
There are plenty of viruses that carry their genetic information in RNA instead of DNA; some of them use dsRNA. “I’m interested in how our work lets us know about how viruses might be killed in different conditions,” she said. Or if viral dsRNA from wastewater could be preserved better at higher pH to help to follow and predict the spread of disease.
And there’s another area, a little different from the rest, in which a better understanding of dsRNA might be useful: unlocking the mysteries of the origin of life on Earth. It’s only conjecture, but it’s something that captured Zhang’s interest.
There is a long-held theory that life on Earth began in hydrothermal vents when smaller molecules came together to form RNA. However, that theory has a fatal flaw: The conditions in these vents would have been alkaline.
“Some scientists think that can’t be possible because RNA would degrade in such conditions,” Zhang said. “But we have found that it’s only true for ssRNA. If we consider dsRNA, at alkaline pH, it can maintain its chemical stability.”
Magnetic sensitivity of cryptochrome 4 from a migratory songbird
by Jingjing Xu, Lauren E. Jarocha, Tilo Zollitsch, Marcin Konowalczyk, Kevin B. Henbest, Sabine Richert, Matthew J. Golesworthy, Jessica Schmidt, Victoire Déjean, Daniel J. C. Sowood, Marco Bassetto, Jiate Luo, Jessica R. Walton, Jessica Fleming, Yujing Wei, Tommy L. Pitcher, Gabriel Moise, Maike Herrmann, Hang Yin, Haijia Wu, Rabea Bartölke, Stefanie J. Käsehagen, Simon Horst, Glen Dautaj, Patrick D. F. Murton, Angela S. Gehrckens, Yogarany Chelliah, Joseph S. Takahashi, Karl-Wilhelm Koch, Stefan Weber, Ilia A. Solov’yov, Can Xie, Stuart R. Mackenzie, Christiane R. Timmel, Henrik Mouritsen, P. J. Hore in Nature
A bird’s-eye view may take on new meaning thanks to Army-funded research. Scientists found that a protein in bird’s retinas is sensitive to the Earth’s magnetic field thus guiding its migratory patterns. That finding could be key to Army navigation of both autonomous and manned vehicles where GPS is unavailable.
For decades, scientists have been investigating how animals such as birds, sea turtles, fish and insects sense the Earth’s magnetic field and use it to find their way. Researchers at the Universities of Oxford and Oldenburg were the first to demonstrate that a protein in birds’ retinas is sensitive to magnetic fields and may be a long-sought sensor for biological navigation.
The team discovered that the magnetic sense of migratory birds such as European robins is based on a specific light-sensitive protein in the eye. The research identified the protein that the scientists believe allows these songbirds to detect the direction of the Earth’s magnetic field and navigate their migration.
“This research not only demonstrated that cryptochrome 4 is sensitive to magnetic fields, but importantly also identified the molecular mechanism underlying this sensitivity,” Dr. Stephanie McElhinny, a program manager at the laboratory. “This fundamental knowledge is critical for informing future technology development efforts aimed at exploiting this mechanism for highly sensitive magnetic field sensors that could enable Army navigation where GPS is unavailable, compromised or denied.”
The researchers extracted the genetic code for the potentially magnetically sensitive cryptochrome 4 and produced the photoactive protein in large quantities using bacterial cell cultures. The team then used a wide range of magnetic resonance and novel optical spectroscopy techniques to study the protein and demonstrate its pronounced sensitivity to magnetic fields.
The team showed that the protein is sensitive to magnetic fields due to electron transfer reactions triggered by absorption of blue light. They believe that these highly-specialized chemical reactions give the birds information about the direction of the Earth’s magnetic field, which acts like a magnetic compass.
“While more research needs to be done to fully understand how cryptochrome 4 senses the weak magnetic field of Earth and how this is ultimately translated into signals that are understood by the migrating bird, this new knowledge is an exciting first step toward potential navigation systems that would rely only on the magnetic field of Earth, unaffected by weather or light levels,” McElhinny said.
Because the magnetic field modifies the cryptochrome protein in a measurable way, cryptochrome proteins or synthetic molecules that mimic the mechanism of cryptochrome’s magnetic sensing could be used in a future navigation device. Detectable changes in the protein would be decoded to indicate the strength and direction of the magnetic field, and thus the navigational position on Earth.
Proteins like cryptochrome consist of chains of amino acids. Cyrptochrome 4 contains four tryptophan amino acids that are organized in series. According to the research team’s calculations, electrons hop from one tryptophan to the next through the series, generating so-called radical pairs which are magnetically sensitive.
To prove this experimentally, the team from Oldenburg University produced slightly modified versions of the robin cryptochrome, in which each of the tryptophans in turn was replaced by a different amino acid to block the movement of electrons.
Using these modified proteins, the Oxford University chemistry groups experimentally demonstrated that electrons move within the cryptochrome as predicted in the calculations and that the generated radical pairs are essential to explain the observed magnetic field effects.
The team also expressed cryptochrome 4 from chickens and pigeons, which do not migrate. The researchers found that the protein is more magnetically sensitive in the migratory birds than either the chickens or pigeons.
“We think these results are very important because they show for the first time that a molecule from the visual apparatus of a migratory bird is sensitive to magnetic fields,” said Professor Henrik Mouritsen, Institute of Biology and Environmental Sciences at Oldenburg University.
But, he adds, this is not definitive proof that cryptochrome 4 is the magnetic sensor the team is looking for. In all experiments, the researchers examined isolated proteins in the laboratory and the magnetic fields used were also stronger than the Earth’s magnetic field.
“It therefore still needs to be shown that this is happening in the eyes of birds,” Mouritsen said.
Such studies are not yet technically possible; however, the authors think the proteins involved could be significantly more sensitive in their native environment.
In cells in the retina, the proteins are probably fixed and aligned, increasing their sensitivity to the direction of the magnetic field. Moreover, they are also likely to be associated with other proteins that could amplify the sensory signals. The team is currently searching for these as yet unknown interaction partners.
“If we can prove that cryptochrome 4 is the magnetic sensor we will have demonstrated a fundamentally quantum mechanism that makes animals sensitive to environmental stimuli a million times weaker than previously thought possible,” said Peter Hore, professor of Chemistry at the University of Oxford.
Establishment, maintenance, and recall of inflammatory memory
by Samantha B. Larsen, Christopher J. Cowley, Sairaj M. Sajjath, Douglas Barrows, Yihao Yang, Thomas S. Carroll, Elaine Fuchs in Cell Stem Cell
When a tissue experiences inflammation, its cells remember. Pinning proteins to its genetic material at the height of inflammation, the cells bookmark where they left off in their last tussle. Next exposure, inflammatory memory kicks in. The cells draw from prior experience to respond more efficiently, even to threats that they have not encountered before. Skin heals a wound faster if it was previously exposed to an irritant, such as a toxin or pathogen; immune cells can attack new viruses after a vaccine has taught them to recognize just one virus.
Now, a new study describes the mechanism behind inflammatory memory, also commonly referred to as trained immunity, and suggests that the phenomenon may be universal across diverse cell types.
“This is happening in natural killer cells, T cells, dendritic cells from human skin, and epidermal stem cells in mice,” says Samantha B. Larsen, a former graduate student in the laboratory of Elaine Fuchs at The Rockefeller University. “The similarities in mechanism are striking, and may explain the remitting and relapsing nature of chronic inflammatory disorders in humans.”
When thinking about our immune system, we default to specific immunity — that cadre of T cells and B cells trained, by experience or vaccination, to remember the specific contours of the last pathogen that broke into our bodies. But there’s a less specific strategy available to many cells, known as trained immunity. The impact is shorter-lived, but broader in scope. Trained immunity allows cells to respond to entirely new threats by drawing on general memories of inflammation.
Scientists have long suspected that even cells that are not traditionally involved in the immune response have the rudimentary ability to remember prior insults and learn from experience. The Fuchs lab drove this point home in a 2017 study by demonstrating that mouse skin that had recovered from irritation healed 2.5 times faster than normal skin when exposed to irritation at a later date.
One explanation, the Fuchs team proposed, could be epigenetic changes to the skin cell genome itself. During inflammation, regions of DNA that are usually tightly coiled around histone proteins unravel to transcribe a genetic response to the attack. Even after the dust settles, a handful of these memory domains remain open — and changed. Some of their associated histones have been modified since the assault, and proteins known as transcription factors have latched onto the exposed DNA. A once naïve cell is now raring for its next fight. But the molecular mechanism that explained this process, and how the cell could use it to respond to types of inflammation and injury that it had never seen before, remained a mystery.
So the Fuchs lab once again exposed mice skin to irritants, and watched as stem cells in the skin changed. “We focused on the regions in the genome that become accessible during inflammation, and remain accessible afterwards,” says Christopher Cowley, a graduate student in the Fuchs lab. “We call these regions memory domains, and our goal was to explore the factors that open them up, keep them open and reactivate them a second time.”
They observed about 50,000 regions within the DNA of the stem cells that had unraveled to respond to the threat, but a few months later only about 1,000 remained open and accessible, distinguishing themselves as memory domains. Interestingly, many of these memory domains were the same regions that had unraveled most prodigiously in the early days of skin inflammation.
The scientists dug deeper and discovered a two-step mechanism at the heart of trained immunity. The process revolves around transcription factors, proteins which govern the expression of genes, and hinges on the twin transcription factors known as JUN and FOS.
The stimulus-specific STAT3 transcription factor responds first, deployed to coordinate a genetic response to a particular genre of inflammation. This protein hands the baton to JUN-FOS, which perches on the unspooled genetic material to join the melee. The specific transcription factor that sounded the original alarm will eventually return home; FOS will float away as the tumult quiets down. But JUN stands sentinel, guarding the open memory domain with a ragtag band of other transcription factors, waiting for its next battle.
When irritation strikes again, JUN is ready. It rapidly recruits FOS back to the memory domain, and the duo charges into the fray. This time, no specific transcription factor is necessary to respond to a particular type of inflammation and get the ball rolling. The system unilaterally activates in response to virtually any stress — alacrity that may not always benefit the rest of the body.
Trained immunity may sound like a boon to human health. Veteran immune cells seem to produce broader immune responses; experienced skin cells should heal faster when wounded. But the same mechanism that keeps cells on high alert may instill a sort of molecular paranoia in chronic inflammation disorders. When the Fuchs lab examined data collected from patients who suffer from systemic sclerosis, for instance, they found evidence that JUN may be sitting right on the memory domains of affected cells, itching to incite an argument in response to even the slightest disagreement.
“These arguments need not always be disagreeable, as animals benefit by healing their wounds quickly and plants exposed to one pathogen are often protected against others,” says Fuchs. “That said, chronic inflammatory disorders may owe their painful existence to the ability of their cells to remember, and to FOS and JUN, which respond universally to stress.”
The scientists hope that shedding light on one possible cause of chronic inflammatory disease may help researchers develop treatments for these conditions. “The factors and pathways that we identify here could be targeted, both in the initial disease stages and, later, during the relapsing stages of disease,” says Cowley. Larsen adds: “Perhaps these transcription factors could be used as a general target to inhibit the recall of the memories that cause chronic inflammation.”
Plant PIEZO homologs modulate vacuole morphology during tip growth
by Ivan Radin, Ryan A. Richardson, Joshua H. Coomey, Ethan R. Weiner, Carlisle S. Bascom, Ting Li, Magdalena Bezanilla, Elizabeth S. Haswell in Science
Minuscule tunnels through the cell membrane help cells to perceive and respond to mechanical forces, such as pressure or touch. A new study is among the first to directly investigate what one type of these mechanosensitive ion channels is doing in the tip-growing cells in moss and pollen tubes of flowering plants, and how.
Biologists led by Elizabeth Haswell at Washington University in St. Louis discovered that so-called PIEZO channels are not found along the plasma membrane in plant cells as they are in animal cells.
Instead, they observed that PIEZO channels have retreated into the plant cell, an unexpected discovery. PIEZO channels are found deeper within the cell, in the membranes of vacuoles — the large, intracellular organelles that help maintain cell turgor and fulfill a number of other roles in the plant cell.
“PIEZO channels in plants play a dramatic and critical role in regulating the shape of the vacuole and how much membrane there is,” said Haswell, a professor of biology in Arts & Sciences and a Howard Hughes Medical Institute-Simons Faculty Scholar.
“This is the first example of PIEZO channels involved in regulating organelle morphology,” she said. “The data we present could lead to new lines of investigation for both plant and animal PIEZO homologs.”
As the name suggests, mechanosensitive ion channels are paths, or tunnels, through cell membranes that respond to mechanical forces. Under certain forces a channel opens, allowing the flow of ions across the membrane.
In humans, PIEZO channels are essential for life; without them, cell development halts. They are recognized for their role in perceiving light touch, shear force and compressive force. Dysfunction in PIEZO channels has been linked to multiple human diseases.
PIEZO channels were first identified in plant genomes in 2010. After a decade of research on animal homologs, this new research shines a spotlight on plant cells and explores how they differ from animal cells. Other research teams have recently shown that PIEZO channels are involved in mechanical sensing in plant roots.
The researchers made their initial discoveries using the tip-growing cells of a somewhat atypical model plant, spreading earthmoss (Physcomitrium patens). But the scientists were able to extend their findings beyond moss to cells from other distantly related plants, including in pollen tubes in a classic model, the flowering plant Arabidopsis thaliana.
“Mosses are one of the groups that comprise the bryophytes, which are the second largest land plant lineage,” said Ivan Radin, a research scientist in the Haswell laboratory and first author of the new paper.
“When we can show that the same thing happens both in moss and a flowering plant, as we did here, the most likely conclusion is that the process is ancestral — it’s at least as old as the land plants are,” Radin said, noting that land plants colonized Earth about a half a billion years ago.
Radin became the Haswell laboratory’s de facto moss specialist with coaching from co-author Magdalena Bezanilla, a professor of biological sciences at Dartmouth University. Bezanilla previously worked with Washington University’s Ralph Quatrano, emeritus dean and the Spencer T. Olin Professor Emeritus of Biology, who was an early adopter of moss.
As a next step in this research, scientists in the Haswell laboratory are now conducting additional experiments to show how external and internal forces directly affect PIEZO channels in moss cells.
“Plant PIEZO channels are likely to be controlled by membrane tension in plants the same way they are in animals,” Haswell said. The scientists are also exploring the evolution of these channels in algae.
Now they know where PIEZO channels are found in the cell, Haswell and her team are poised to find out what these proteins are doing in the vacuoles.
“We are looking at how PIEZO channel activation results in membrane elaboration and how it is regulated,” Haswell said. “We want to know how the localization evolved and what it does in other cell types. We plan to compare and contrast the structure and function with the animal channels and in organisms across the green lineage.”
Directly Reprogrammed Neurons as a Tool to Assess Neurotoxicity of the Contaminant 4-Hydroxy-2′,3,5,5′-tetrachlorobiphenyl (4′OH-CB72) in Melon-Headed Whales
by Mari Ochiai, Hoa Thanh Nguyen, Nozomi Kurihara, Masashi Hirano, Yuko Tajima, Tadasu K. Yamada, Hisato Iwata in Environmental Science & Technology
Whales accumulate large burdens of environmental pollutants that threaten their survival and health. Toxicological studies on cetacean species have been extremely challenging because invasive studies are restricted by legal and ethical considerations and sampling of wild cetaceans is highly opportunistic. Although model animal studies can provide data from practical experiments, extrapolating the toxicological effects to cetaceans is limited due to the large interspecies susceptibility to chemical exposure. The types of whale cells that can be cultured are limited, and cell-specific assays for whales have not been developed. A research team of the Center for Marine Environmental Studies (CMES) of Ehime University, Japan succeeded in direct reprogramming the fibroblasts of stranded melon-headed whales (Peponocephala electra) to neurons, not through the induction of pluripotent stem cells (iPSCs), but by using a cocktail of small compounds. Using whale induced neurons, they have investigated the neurotoxicity of an environmental pollutant on cetacean neurons for the first time.
The research team obtained tissue samples from melon-headed whales mass stranded along the coast of Hokota-city, Ibaraki, Japan. After a few weeks of treatment with a cocktail of small compounds, the morphology of the fibroblast cells derived from the melon-headed whale tissues changed to neuron-like cells. Reprogramming of the fibroblasts to neurons, induced neuronal cells (iNCs), was confirmed by positive signals for neuronal markers: beta-III tubulin (Tuj-1) and microtubule associated protein 2 (MAP2), and negative signals for astrocyte and oligodendrocyte markers: glial fibrillary acidic protein (GFAP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), respectively. Transcriptome analysis of the whale iNCs also supported the success in reprogramming, showing downregulation of a fibroblast marker elastin (ELN) and upregulation of neuron-related genes such as synaptic genes: synaptophysin (SYP) and stathmin 3 (STMN3).
Apoptosis was measured by detecting nuclear chromatin fragmentation by TUNEL assay. Over 80% of whale iNCs have led to apoptosis after 24hr exposure to 20?M 4'OH-CB72, with apoptosis-positive cells increasing 1.8–2.4 times compared to vehicle controls.
Upregulation of the genes related to apoptosis in whale iNCs was also confirmed by transcriptome analysis. Genes such as apoptosis inducing factor mitochondria associated 1 (AIFM1), BH3 interacting domain death agonist (BID), and tumor necrosisfactor (TNF) receptor associated factor 2 (TRAF2) were upregulated in whale iNCs. On the other hand, cell survival-related genes were downregulated in whale iNCs. Additionally, many genes involved in neurodegenerative diseases such as Alzheimer’s disease, amyotrophic lateral sclerosis, and Huntington’s disease were altered in whale iNCs exposed to 4'OH-CB72.
Bioinformatics analyses using differentially expressed genes upon exposure to 4'OH-CB72 suggested that the cellular signaling pathways of mitochondrial dysfunction, chromatin degradation, axonal transport, and ubiquitin proteasome system were disrupted by this pollutant. These effects ultimately lead to neurodegeneration through neuronal apoptosis and cell death.
Since cetaceans are chronically exposed to a variety of environmental pollutants, not only 4'OH-CB72, but also other PCBs, the neurotoxicity of other compounds is also of concern. This approach may be useful for other marine mammals for which there is yet no effective means of neurotoxicity testing.
Talin mechanosensitivity is modulated by a direct interaction with cyclin-dependent kinase-1
by Rosemarie E. Gough, Matthew C. Jones, Thomas Zacharchenko, Shimin Le, Miao Yu, Guillaume Jacquemet, Ste P. Muench, Jie Yan, Jonathan D. Humphries, Claus Jørgensen, Martin J. Humphries, Benjamin T. Goult in Journal of Biological Chemistry
Research from the University of Kent’s School of Biosciences and the University of Manchester has uncovered an essential mechanism coordinating the processes of cell division and adhesion within humans. This discovery has profound potential for advancing understanding of cell adhesion signalling in cancerous tumour progression and metastasis.
The research identifies the long sought link within the cell cycle between the mechanism for cell division, the proliferation that enables all living organisms to function and regenerate, and the cell adhesion that holds them in the correct position within the organism’s structure.
For cell division to occur inside humans, the cell must release its adhesions to the surroundings at the exact moment the cell starts to divide. This synchronisation of the cell adhesion and the cell cycle is critical for the correct functioning of cells in tissues and to prevent uncontrolled cell division in processes such as cancer.
Researchers found that CDK1, the master regulator of the cell cycle binds directly to, and modifies, the core protein talin that is essential to the process of cell adhesion. This interaction represents a coupling of the cell proliferation and adhesion processes. This indicates a unifying mechanism by which the processes of cell division and adhesion are controlled.
Discovering the initial mechanism of this vital process in the tissues of humans is the first-step in a new branch of understanding health issues relating to the cell cycle, including cancerous tumours.
Dr Ben Goult, Reader in Biochemistry at the University of Kent and a Principal Investigator of the paper said: ‘The potential of this discovery is huge as it provides a new understanding of how cell division is coordinated within the confines of a complex multicellular organism. Cell division needs to be tightly coupled to the cell adhesion to allow our cells to divide without disrupting the integrity of our tissues and organs. This research is vital in our understanding of other cellular diseases and of cancer’s ability to spread within the human body.’
Host-specific gene expression as a tool for introduction success in Naupactus parthenogenetic weevils
by Ava Mackay-Smith, Mary Kate Dornon, Rosalind Lucier, Anna Okimoto, Flavia Mendonca de Sousa, Marcela Rodriguero, Viviana Confalonieri, Analia A. Lanteri, Andrea S. Sequeira in PLOS ONE
Without the benefits of evolutionary genetic variation that accompany meiotic reproduction, how does an asexual invasive species adapt over time to a new environment to survive? In all-female weevil species that produce only female offspring from unfertilized eggs, the insects’ survival techniques have led to the surprising discovery that these creatures can pass down gene regulation changes to future generations.
New research from Wellesley College has found that two types of weevils, common yet invasive beetles in many parts of the world, have been using epigenetic changes to adapt and respond to different toxins in the plants they eat. The findings have implications for how we consider asexual invaders and how successful they can be because of gene regulation.
The researchers, led by Andrea Sequeira, Wellesley College Gordon and Althea Lang, Professor of Biological Sciences, collected samples of parthenogenetic, invasive, and polyphagous weevils, Naupactus cervinus and N. leucoloma, from Florida, California, and Argentina over the course of five years, starting in 2015. Despite being from different locations within the United States where they have been introduced, often through commerce, the weevils are asexual and genetically identical. Yet the team found that they have uniquely adapted to produce different proteins that allow them to eat and digest a variety of plants, even those that produce toxins.
Sequeira worked with a talented team: Ava Mackay-Smith, Mary Kate Dornon, Rosalind Lucier, Anna Okimoto, and Flavia Mendonca de Sousa from Wellesley College, and Marcela Rodriguero, Viviana Confalonieri, Analia Lanteri from the University of Buenos Aires and the Museo de Ciencias Naturales in La Plata, Argentina. Together, they analyzed patterns of gene expression in three gene categories that can mediate weevil-host plant interactions through identification of suitable host plants, short-term acclimation to host plant defenses, and long-term adaptation to host plant defenses and their pathogens.
“We found that some host plant groups, such as legumes, appear to be more taxing for weevils and elicit a complex gene expression response,” Sequeira said. “However, the weevil response to taxing host plants shares many differentially expressed genes with other stressful situations, such as organic cultivation conditions and transition to novel hosts, suggesting that there is an evolutionarily favorable shared gene expression regime for responding to different types of stressful situations.”
“We also found that mothers are able to ‘prime’ their young with these epigenetic changes,” lead author and 2020 Wellesley College alumna Ava Mackay-Smith said. “Originally, we thought that these changes would only be seen in a single generation. When we studied larvae, who do not yet have mouths or eat plants, we found evidence of the same proteins and adaptations from their mothers.”
Sequeira noted this finding is especially important because classic understanding has been that in both sexual and asexual reproduction, all epigenetic marks are erased between generations and each generation starts over.
Mackay-Smith believes that having a better understanding of epigenetic changes in invasive, asexual species may eventually help regulate or mitigate their potential negative impact on an environment, native plants, or crops, for example. “Knowing what is in this insect’s repertoire, you could imagine that since we’ve now identified the proteins that are regulated differently, you could target a specific protein and design a targeted pesticide that removes only that species of weevil, without harming other native insects or fauna.”
Both Mackay-Smith and Sequeira are excited to see that perhaps genetic variation is not the only form of heritable variation for natural selection to act upon and that epigenetic processes may increase the evolutionary potential of organisms in response to stress and other environmental challenges — adaptations that could be relevant in the context of climate change.
Multicellularity and sex helped shape the Tree of Life
by Lian Chen, John J. Wiens in Proceedings of the Royal Society B: Biological Sciences
There are huge differences in species numbers among the major branches of the tree of life. Some groups of organisms have many species, while others have few. For example, animals, plants and fungi each have over 100,000 known species, but most others — such as many algal and bacterial groups — have 10,000 or less.
A new University of Arizona-led study tested whether sexual reproduction and multicellularity might help explain this mysterious pattern.
“We wanted to understand the diversity of life,” said paper co-author John Wiens, a professor in the Department of Ecology and Evolutionary Biology. “Why are most living things animals, plants and fungi?”
To address this, Wiens worked with a visiting scientist in his lab, Lian Chen from Nanjing Forestry University in China. They estimated rates of species proliferation in 17 major groups that spanned all living organisms, including bacteria, protists, fungi, plants and animals. The hard part was to estimate how many species in each group were multicellular versus unicellular and how many reproduced sexually versus asexually. For five years, Chen sifted through more than 1,100 scientific papers and characterized the reproductive modes and cellularity of more than 1.5 million species.
They found that both multicellularity and sexual reproduction helped explain the rapid proliferation of animal, plant and fungal species. The rapid proliferation of these three groups explains why they now include more than 90% of Earth’s known species.
The duo also found that the rapid proliferation of sexual species may help explain the “paradox of sex.” The paradox is why so many species reproduce sexually, despite the disadvantages of sexual reproduction.
“For sexual species, only half the individuals are directly producing offspring. In an asexual species, every individual is directly producing offspring,” Wiens said. “Sexual reproduction is not as efficient. Another disadvantage of sexual reproduction is that you do need two individuals to make something happen, and those two individuals have to be the right sexes. Asexual species, on the other hand, only need one individual to reproduce.”
Chen and Wiens found a straightforward answer to the paradox of sex. The reason why there are so many sexual species is because sexual species actually proliferate more rapidly than asexual species. This had not been shown across all of life before.
They also found that another explanation for the large number of sexual species is that sexual reproduction and multicellularity are strongly associated across the tree of life, and that multicellularity helps drive the large number of sexual species.
“Multicellularity is actually more important than sexual production. We did a statistical analysis that showed it is probably at least twice as important for explaining these patterns of diversity as sexual reproduction,” Wiens said.
And while this study alone can’t pinpoint exactly why multicellularity is so important, researchers have previously suggested that it has to do with the variety of cell types within a multicellular organism.
“If you’re a single cell, there’s not much variety there,” Wiens said. “But multicellularity allows for different tissues or cell types and allows for diversity. But how exactly it leads to more rapid proliferation will need more study.”
Chen and Wiens also tested how their conclusions might change if most living species on Earth were species of bacteria that are still unknown to science.
“Most bacteria are unicellular and asexual. But because bacteria are much older than plants, animals and fungi, they have not proliferated as rapidly, even if there are billions of bacterial species,” Wiens said. “Therefore, multicellularity and sexual reproduction still explain the rapid proliferation of animals, plants and fungi.”
Future work will be needed to understand how multicellularity and sexual reproduction drive biodiversity. Wiens is also interested in how some groups are both multicellular and reproduce sexually yet don’t proliferate rapidly.
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