Spider silk is spun by silkworms for the first time, offering a green alternative to synthetic fibers

Peer-Reviewed Publication

CELL PRESS

 

IMAGE: SILK FIBERS PRODUCED BY TRANSGENIC SILKWORMS view more 

CREDIT: JUNPENG MI

Scientists in China have synthesized spider silk from genetically modified silkworms, producing fibers six times tougher than the Kevlar used in bulletproof vests. The study, published September 20 in the journal Matter, is the first to successfully produce full-length spider silk proteins using silkworms. The findings demonstrate a technique that could be used to manufacture an environmentally friendly alternative to synthetic commercial fibers such as nylon.

“Silkworm silk is presently the only animal silk fiber commercialized on a large scale, with well-established rearing techniques,” said Mi. “Consequently, employing genetically modified silkworms to produce spider silk fiber enables low-cost, large-scale commercialization.”

Scientists have eyed spider silk as an enticingly sustainable alternative to synthetic fibers, which can release harmful microplastics into the environment and are often produced from fossil fuels that generate greenhouse gas emissions. But turning to nature for alternatives isn’t without challenges. Previously developed processes for spinning artificial spider silk have struggled to apply a surface layer of glycoproteins and lipids to the silk to help it withstand humidity and exposure to sunlight—an anti-aging “skin layer” that spiders apply to their webs.

Genetically modified silkworms offer a solution to this problem, says Mi, since silkworms coat their own fibers with a similar protective layer.

“Spider silk stands as a strategic resource in urgent need of exploration,” said Junpeng Mi, a PhD candidate at the College of Biological Science and Medical Engineering at Donghua University and the first author of the study. “The exceptionally high mechanical performance of the fibers produced in this study holds significant promise in this field. This type of fiber can be utilized as surgical sutures, addressing a global demand exceeding 300 million procedures annually.”

The spider silk fibers could also be used to create more comfortable garments and innovative types of bulletproof vests, says Mi, and they may have applications in smart materials, the military, aerospace technology, and biomedical engineering.

To spin spider silk from silkworms, Mi and his team introduced spider silk protein genes into the DNA of silkworms so that it would be expressed in their glands using a combination of CRISPR-Cas9 gene editing technology and hundreds of thousands of microinjections into fertilized silkworm eggs. The microinjections posed “one of the most significant challenges” in the study, said Mi, but when he saw the silkworms’ eyes glowing red under the fluorescence microscope—a sign that the gene editing had been successful—he was overjoyed.

“I danced and practically ran to Professor Meng Qing’s office to share this result,” said Mi. “I remember that night vividly, as the excitement kept me awake.”

The researchers also needed to perform “localization” modifications on the transgenic spider silk proteins so that they would interact properly with proteins in the silkworm glands, ensuring that the fiber would be spun properly. To guide the modifications, the team developed a “minimal basic structure model” of silkworm silk.

“This concept of ‘localization,’ introduced in this thesis, along with the proposed minimal structural model, represents a significant departure from previous research,” says Mi. “We are confident that large-scale commercialization is on the horizon.”

In the future, Mi plans to use insights into the toughness and strength of spider silk fibers developed in the current study to develop genetically modified silkworms that produce spider silk fibers from both natural and engineered amino acids.

“The introduction of over one hundred engineered amino acids holds boundless potential for engineered spider silk fibers,” says Mi.

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This work was supported by the National Natural Science Foundation of China, Key Projects of Science and Technology Commission of Shanghai Municipality, the International Cooperation Projects of Science and Technology Commission of Shanghai Municipality, and Fundamental Research Funds for the Central Universities.

Matter, Mi et al. “High-strength and ultra-tough whole spider silk fibers spun from transgenic silkworms” https://cell.com/matter/fulltext/S2590-2385(23)00421-6

Matter (@Matter_CP), published by Cell Press, is a new journal for multi-disciplinary, transformative materials sciences research. Papers explore scientific advancements across the spectrum of materials development—from fundamentals to application, from nano to macro. Visit: https://www.cell.com/matter. To receive Cell Press media alerts, please contact press@cell.com.

Image of forced reel silk

CREDIT

Junpeng Mi

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JOURNAL

Matter

DOI

10.1016/j.matt.2023.08.013 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

High-strength and ultra-tough whole spider silk fibers spun from transgenic silkworms

ARTICLE PUBLICATION DATE

20-Sep-2023

 

Newfound brain circuit explains why infant cries prompt milk release

Peer-Reviewed Publication

NYU LANGONE HEALTH / NYU GROSSMAN SCHOOL OF MEDICINE

Hearing the sound of a newborn’s wail can trigger the release of oxytocin, a brain chemical that controls breast-milk release in mothers, a new study in rodents shows. Researchers found that once prompted, this flood of hormones continues for roughly five minutes before tapering off, enabling mothers to feed their young until they are sated or begin crying again.

Led by researchers at NYU Grossman School of Medicine, the study explored a centuries-old observation in humans and other mammals that when a baby begins a feeding session, its cries alone can prompt its mother to release breast milk. Studies dating back decades have shown that such calls for food, and not suckling itself, prompts the largest oxytocin surges. However, the mechanisms behind and purpose for this wail-to-milk pipeline had until now remained unclear.

According to the findings, publishing online Sept. 20 in the journal Nature, when a mouse pup starts crying, sound information travels to an area of its mother’s brain called the posterior intralaminar nucleus of the thalamus (PIL). This sensory hub then sends signals to oxytocin-releasing brain cells (neurons) in another region called the hypothalamus, a control center for hormone activity.

Most of the time these hypothalamus neurons are “locked down” by proteins that act as gatekeepers to prevent false alarms and wasted milk. After 30 seconds of continuous crying, however, signals from the PIL were found to build up and overpower these inhibitory proteins, setting off oxytocin release.

“Our findings uncover how a crying infant primes its mother’s brain to ready her body for nursing,” said study co-lead author Habon Issa, a graduate student at NYU Langone Health. “Without such preparation, there can be a delay of several minutes between suckling and milk flow, potentially leading to a frustrated baby and stressed parent.”

The results also revealed that the oxytocin boost only occurs in mother mice and not in females who have never given birth. In addition, the mothers’ brain circuitry only responded to her pups’ cries and not to computer-generated tones designed to mimic natural wails.

According to Issa, the study offers the first description of how sensory experiences like hearing directly activate oxytocin neurons in mothers. She notes that the scientists used a relatively new kind of molecular sensor called iTango to measure actual oxytocin release from brain cells in real time. Previously, she says, researchers could only take indirect measurements using proxies because the hormone degrades quickly given its small size.

For the study, the research team examined brain-cell activity in dozens of female mice. Then, in a form of “reverse engineering,” they traced how sound information travels through different areas of the brain to trigger milk flow.

Next, the team explored how this circuit affects parenting behavior. Normally, when pups stray or are removed from their nest, mothers will quickly retrieve them no matter how many times this occurs, says Issa. However, when the researchers chemically blocked the PIL from communicating with oxytocin neurons, the mice eventually tired and stopped fetching their young. Once the system was turned back on, the mothers pushed through their fatigue and continued caring for the infants.

“These results suggest that the crying-prompted brain circuit is not only important for nursing behavior, but also for maintaining a mother’s attention over time and encouraging effective care of her young even when she is exhausted,” said study senior author Robert Froemke, PhD. Froemke is the Skirball Foundation Professor of Genetics in the Department of Neuroscience and Physiology at NYU Langone.

Also a professor in the Department of Otolaryngology÷Head and Neck Surgery at NYU Langone, Froemke adds that learning how the oxytocin system works (and goes awry) in our own species may offer new ways to help human mothers who want to breastfeed but struggle to do so.

Froemke, a member of NYU Langone’s Neuroscience Institute, cautions that the researchers did not measure lactation itself, only the hormone release that prompts it.

Funding for the study was provided by National Institutes of Health grants T32MH019524, P01NS107616, and DP1MH119428. Further funding was provided by the Natural Sciences and Engineering Research Council of Canada PGS-D Fellowship and a Howard Hughes Medical Institute Faculty Scholarship.

In addition to Issa and Froemke, former NYU investigator Silvana Valtcheva, PhD, now at the University of Cologne in Germany, served as the study co-lead author. Other NYU Langone investigators involved in the study were Chloe Blair-Marshall, BS; Kathleen Martin, BS; and Yiyao Zhang, PhD. Additional study authors include Kanghoon Jung, PhD; and Hyung-Bae Kwon, PhD, at Johns Hopkins University in Baltimore, Md.

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JOURNAL

Nature

DOI

10.1038/s41586-023-06540-4 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Neural circuitry for maternal oxytocin release induced by infant cries

ARTICLE PUBLICATION DATE

20-Sep-2023

 

CUNY ASRC photonics team part of a $30 million National Science Foundation Center established to investigate new frontiers of sound science

Grant and Award Announcement

ADVANCED SCIENCE RESEARCH CENTER, GC/CUNY

NEW YORK, September 7, 2023 — The National Science Foundation has granted a multi-institutional team $30 million over five years to establish a new NSF Science and Technology Center. The New Frontiers of Sound Science and Technology Center, which comes with an additional $30 million funding option over the following five years, will bring together researchers working in topological acoustics. The team is led by principal investigator Pierre Deymier, a University of Arizona (UArizona) professor of materials science and engineering in the College of Engineering. Co-principal investigators, including Andrea Alù, founding director of the Advanced Science Research Center at the CUNY Graduate Center’s (CUNY ASRC) Photonics Initiative, Distinguished Professor and Einstein Professor of Physics at the CUNY Graduate Center; Sara Chavarria, of UArizona; Chiara Daraio of the California Institute of Technology; and Massimo Ruzzene of the University of Colorado Boulder.

Professor Alù of the CUNY ASRC will lead the team’s research on topological acoustics and its applications to wireless communications and sound technologies. With topological acoustics, researchers exploit the properties of sound in ways that could vastly improve computing, telecommunications, and sensing. Applications could include reaching quantum-like computing speeds, reducing the power usage of smartphones, and sensing changes in aging infrastructure or the natural environment due to climate change.

“This newly funded center brings together a synergistic team to leverage the initial proof-of-concept discoveries that my group and others have been working on in the area of topology for the last several years,” said Alù. “Our collective work aims to push these concepts into groundbreaking scientific and engineering advances that we expect to impact wireless technologies, energy-efficient computing, bio-medical and environmental sensing, and other important societal benefits. These highly interdisciplinary activities are very well suited with the spirit of our mission at the  CUNY ASRC.”

“Today’s science is nearly always collaborative, and groundbreaking work requires cooperation and collegiality, such as that seen in proposing this NSF center across the participating research-leading institutions, including the CUNY ASRC,” said Mark Hauber, the new executive director of the CUNY ASRC.

"We all know technologies such as the loudspeaker or the microphone, but we also use sound for sensing environments, such as with sonar and ultrasound medical imaging, and for data transmission and processing every day in your smartphone," said center director and project principal investigator Deymier. "However, the quiet revolution advancing sound science and technology is afoot. And that is where the new center comes in."

"Scientific discovery is the engine that drives human progress and underlies all of the technologies that we benefit from today," said NSF Director Sethuraman Panchanathan. "NSF's Science and Technology Centers enable our most creative scientists and engineers to open new vistas of scientific inquiry and make the discoveries that will keep the U.S. in the forefront of scientific discovery.”

Mapping sound to space

Using topological acoustics is a sophisticated way of looking at sound that maps sound waves to an abstract multidimensional space, called a Hilbert Space, to examine their geometry. By examining sound in this way, scientists can see and manipulate attributes of sound waves that aren't visible in traditional acoustics.

Topological acoustics exploits attributes of sound waves that so far have remained hidden. It harnesses the full power of acoustic waves, enabling extraordinary properties of sound such as sound waves that mimic quantum waves or that can hit a hard surface without generating an echo. These properties can affect a huge number of technologies.

To investigate sound through a topological acoustics lens, scientists form a vector by using all of the points in space that a sound travels through as graph points on the Hilbert Space. The angle of this amplitude vector is known as the geometric phase and provides a visual representation of the geometry of sound.

A simplified example is if a sound is traveling through a room and an object is moved, added, or removed, the effect on the sound may not be noticeable when observed through the lens of traditional acoustics, such as frequency. But it could be seen when examined with topological acoustics, because such minor changes alter the geometry of the sound. New discoveries made by the team could supercharge the field of acoustics by allowing researchers to see information they currently cannot.

An array of applications

This improved understanding of acoustic properties could lead to new computing methods, vastly improved telecommunications, and new sensing capabilities for fields such as environmental science and medicine.

• A Quantum Analog – Topological acoustics researchers could take the billions of data points they map from a sound field and use them as input data for computing, creating a system that controls these data points with extremely high precision. Quantum computing exploits unique relationships, such as entanglement, between units of light called photons. But, with topological acoustics, researchers could form analogous relationships between units of sound called phonons to reap the same benefits. 
• Telecommunications — Devices such as cell phones contain acoustic components that convert electromagnetic waves into acoustic waves and then electrical signals. Because acoustic waves are smaller, they can pass through tiny filtering mechanisms that deliver the correct signal. At higher speeds and capabilities, like 5G and 6G, more filtering mechanisms are required. Engineers and scientists can use topological acoustics to build environments where sound passes through with less energy loss, using less power to increase battery life.
• Sensing – While using sound waves in telecommunications involves preventing the sound waves from scattering as much as possible, sensing uses this scattering to its advantage. The precision of topological acoustics could allow for unparalleled sensitivity in sensing things like disease in tissue, defects in buildings, dryness of soil in fire-prone forests, and the thawing of permafrost in the arctic.

Educational element

Those who haven't heard of topological acoustics aren't alone. That is one big reason the center is providing training and education across multiple disciplines and to people from different backgrounds. Establishing a common language for experts in fields ranging from materials science and electrical engineering to geosciences and mathematics will help the world benefit from the work, those involved in the project say.

The researchers will write a textbook and accompanying digital resources about topological acoustics and launch a center-scale Research Experience and Mentorship, or REM, program to provide opportunities for students underrepresented in STEM to access mentoring and research experience in topological acoustics.

"As a Latina first-generation college graduate, it is important to me that the center emphasizes how committed we are to being inclusive of diverse sciences that align with TA (topological acoustics) work but also inclusive of diverse cultural experiences and backgrounds of our research, education, and student community," said co-principal investigator Chavarria. "The outcome we expect is that this field of TA will be one that represents the world's needs, because we will have trained students of diverse backgrounds to be the future TA scientists, engineers, leaders, and educators."

Center partners include CUNY ASRC; CalTech; Georgia Tech; Spelman College; University of Alaska Fairbanks; University of California, Los Angeles; the University of Colorado Boulder; and Wayne State University.

 

About the Advanced Science Research Center at the CUNY Graduate Center
The Advanced Science Research Center at the CUNY Graduate Center (CUNY ASRC) is a world-leading center of scientific excellence that elevates STEM inquiry and education at CUNY and beyond. The CUNY ASRC’s research initiatives span five distinctive, but broadly interconnected disciplines: nanoscience, photonics, neuroscience, structural biology, and environmental sciences. The center promotes a collaborative, interdisciplinary research culture where renowned and emerging scientists advance their discoveries using state-of-the-art equipment and cutting-edge core facilities.

About the Graduate Center of The City University of New York
The CUNY Graduate Center is a leader in public graduate education devoted to enhancing the public good through pioneering research, serious learning, and reasoned debate. The Graduate Center offers ambitious students nearly 50 doctoral and master’s programs of the highest caliber, taught by top faculty from throughout CUNY — the nation’s largest urban public university. Through its nearly 40 centers, institutes, initiatives, and the Advanced Science Research Center, the Graduate Center influences public policy and discourse and shapes innovation. The Graduate Center’s extensive public programs make it a home for culture and conversation.

 COSMOPOLITANISM

Classic Georgia accent fading fast

Peer-Reviewed Publication

UNIVERSITY OF GEORGIA

A collaborative study between the University of Georgia and Georgia Tech has found the classic Southern accent is undergoing rapid change in Georgia. The instigator? Generation X.

“We found that, here in Georgia, white English speakers’ accents have been shifting away from the traditional Southern pronunciation for the last few generations,” said Margaret Renwick, associate professor in UGA’s Franklin College of Arts and Sciences department of linguistics and lead on the study. “Today’s college students don’t sound like their parents, who didn’t sound like their own parents.”

The researchers observed the most notable change between the baby boomer generation (born 1943 to 1964) and Generation X (born 1965 to 1982), when the accent fell off a cliff.

“We had been listening to hundreds of hours of speech recorded in Georgia and we noticed that older speakers often had a thick Southern drawl, while current college students didn’t,” Renwick said. "We started asking, which generation of Georgians sounds the most Southern of all? We surmised that it was baby boomers, born around the mid-20th century. We were surprised to see how rapidly the Southern accent drops away starting with Gen X.”            

The UGA/Georgia Tech team is the first to identify the accent shift in Georgia.

“The demographics of the South have changed a lot with people moving into the area, especially post World War II," said co-author Jon Forrest, UGA assistant professor in the department of linguistics. Forrest noted that what the researchers see in Georgia is part of a shift noted by others across the entire South, and furthermore, other areas of the U.S. now have similar vowel patterns. “We are seeing similar shifts across many regions, and we might find people in California, Atlanta, Boston and Detroit that have similar speech characteristics,” Forrest said.

The analysis was carried out with recordings of white individuals native to Georgia, born from the late 19th century to the early 2000s. The researchers focused on the way the recorded speakers pronounced vowels. The team found that older Georgians pronounced the word “prize” as prahz and “face” as fuh-eece, but the youngest speakers use prah-eez and fayce. Former UGA graduate student and co-author Joseph A. Stanley, now an assistant professor at Brigham Young University, implemented the statistical modeling.            

“Using transcribed audio, we can use a computer to estimate where you put your tongue in your mouth when you pronounce each vowel, which gives us a quantitative metric of accent,” said Lelia Glass, assistant professor in the School of Modern Languages at Georgia Tech. Marcus Ma, a Georgia Tech undergraduate student working with Glass, devised a tool to streamline the transcription process.

“Changes to the diphthong in ‘prize’ are the oldest characteristic pronunciation in Southern speech, that can be traced back well over 100 years," Renwick said. "The Southern pronunciation of words like ‘face’ emerged in the early 20th century. These are distinctive features of the traditional Southern drawl.”            

While this study used archived as well as new recordings of white speakers from Georgia, as linguistic patterns differ for other ethnic groups, the team is now pursuing the study of cross-generational accents among the Black population.

The exploration of spoken language patterns in Georgia underscores the intricate interplay between generational shifts, societal dynamics and linguistic evolution. As regional accents transform and adapt, the traditional Southern drawl undergoes a remarkable change, with the elongated vowel sound gradually yielding to new patterns favored by younger generations. As this investigation reshapes the understanding of accent variations, it also highlights the need for continued exploration, particularly among diverse ethnic groups.

The study, “Boomer Peak or Gen X Cliff? From SVS to LBMS in Georgia English”, is published in the current issue of the journal Language Variation and Change.

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JOURNAL

Language Variation and Change

DOI

10.1017/S095439452300011X 

ARTICLE TITLE

Boomer Peak or Gen X Cliff? From SVS to LBMS in Georgia English

Intellectual disability more common in families with substance use disorder

Peer-Reviewed Publication

KAROLINSKA INSTITUTET

Children of a parent with alcohol or drug use disorder have a greater risk of intellectual disability, even if the problem only lies with the father, researchers from Karolinska Institutet in Sweden report. According to the study, which is published in the journal eClinicalMedicine, preventive measures should be directed at both parents.

It is well known that a woman’s alcohol consumption during pregnancy can increase the risk of her child developing an intellectual disability. Research from Karolinska Institutet now shows that all forms of substance abuse, both in the mother and the father, and not only during pregnancy, can constitute a risk factor.

Have mainly focused on mothers

“Preventative measures, such as educating healthcare professionals and public health recommendations, have focused for decades on mothers with alcohol-related problems,” says Lotfi Khemiri, researcher at the Departments of Medical Epidemiology and Biostatistics and Clinical Neuroscience, Karolinska Institutet. “Our findings highlight the importance of also directing such measures towards fathers with different types of substance use disorder.”

The study, which is based on data from Swedish registries, comprised almost two million babies born between 1978 and 2002 and their parents. The researchers found that 1.2 per cent of babies born to parents without such a disorder were diagnosed with an intellectual disability, compared with 3 per cent of the babies who had one parent with a diagnosis related to a substance use disorder (alcohol or drug abuse).

Higher risk before birth

The elevated risk was greater if the parent had received a diagnosis before or during pregnancy rather than after birth. A substance use disorder diagnosis registered before birth was associated with more than twice the risk of intellectual disability in the baby, regardless of which parent had the diagnosis. The correlation was weaker but still statistically significant after adjustment of socioeconomic factors and psychiatric comorbidity in the parents.

“Since it was an observational study, we can draw no conclusions about the underlying mechanism, but we suspect that both genetic and environmental factors, including harmful effects of substance abuse on foetal development, may play a part,” says Dr Khemiri. “We hope that the results will contribute to the preventative efforts, as well as to the improved diagnosis of children with an intellectual disability and to timely intervention directed both to the child as well as parents in need of substance use disorder treatment.”

Alcohol is a major risk factor

Intellectual disability was observed to be much more likely in alcohol-related problems during pregnancy, where the risk was five and three times higher depending on whether it was the mother or father who had the alcohol use disorder diagnosis.

The study was financed by several bodies, primarily Region Stockholm, Systembolaget (the Swedish government alcohol retail monopoly) and the Fredrik and Ingrid Thuring Foundation. Co-author and KI researcher Henrik Larsson has received research grants from Shire/Takeda and fees from Medice, Shire/Takeda and Evolan Pharma AB, although unconnected to this present study. All other researchers report no conflicts of interest.

Publication: “Parental substance use disorder and risk of intellectual disability in offspring in Sweden: a national register study”, Lotfi Khemiri, Ralf Kuja-Halkola, Henrik Larsson, Agnieszka Butwicka, Magnus Tideman, Brian M. D’Onofrio, Antti Latvala, Paul Lichtenstein, eClinicalMedicine, online 30 August 2023, doi: 10.1016/j.eclinm.2023.102170.

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JOURNAL

EClinicalMedicine

DOI

10.1016/j.eclinm.2023.102170 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Parental substance use disorder and risk of intellectual disability in offspring in Sweden: a national register study

Gene discovery nets FAU researchers U.S. patent for molecular approach to treat addiction

Invention by Randy D. Blakely, Ph.D. and Maureen Hahn, Ph.D., relates to fields of pharmacology, medicine, neuroscience and psychiatry

Business Announcement

FLORIDA ATLANTIC UNIVERSITY

 

IMAGE: RANDY D. BLAKELY, PH.D., AND MAUREEN K. HAHN, PH.D., HAVE RECEIVED A PATENT FROM THE U.S. PATENT AND TRADEMARK OFFICE FOR A NOVEL METHOD TO IDENTIFY THERAPEUTIC AGENTS TO TREAT ADDICTION. view more 

CREDIT: FLORIDA ATLANTIC UNIVERSITY

According to the Substance Abuse and Mental Health Services Administration, approximately 40 million people in the United States had a substance use disorder in 2020. In addition, over the last decade, the prevalence of opioid addition has increased to epidemic levels. Unfortunately, therapeutic interventions for the treatment of addiction remain limited.

Florida Atlantic University’s Randy D. Blakely, Ph.D., and Maureen K. Hahn, Ph.D., have received a patent from the U.S. Patent and Trademark Office for a novel method to identify therapeutic agents to treat addiction. The invention, related to the fields of pharmacology, medicine, neurology and psychiatry, targets the protein MBLAC1, which the Blakely lab identified as the mammalian form of a gene the group first identified in worms as a modifier of signaling by the neurotransmitter dopamine. 

“The majority of drug addiction research has focused on dopamine signaling and how changes downstream of dopamine action eventually lead to compulsive drug seeking,” said Blakely, executive director of the FAU Stiles-Nicholson Brain Institute, the David J.S. Nicholson Distinguished Professor in Neuroscience, and a professor of biomedical science in FAU’s Schmidt College of Medicine. “However, we found evidence in the worm model C. elegans that a gene expressed in glial cells supports the health and function of dopamine neurons and suspected its actions in humans might also relate to addiction.”

Glia are non-neuronal cells in the brain and peripheral nervous system well known to support neuronal metabolism and the rapid transmission of impulses.

“We now know that glial cells support brain function in many more ways, including aspects of the plasticity and drug responses of nearby neurons. Dopamine neurons are no exception,” said Blakely.

Over the past two decades, the Blakely lab has utilized the simple but powerful worm model for its ability to yield insights into the genes and proteins that regulate dopamine signaling. In 2012, the group identified a new gene they named swip-10, as the loss of this gene produces “Swimming-induced paralysis” or Swip. DNA analysis of swip-10 revealed conserved sequences that comprise a Metallo-b-lactamase Domain (MBD), an element that was also found in an uncharacterized human gene termed MBLAC1. 

“Metallo-b-lactamases are well known to microbiologists for the ability of bacteria to degrade antibiotics such as penicillin and thereby contribute to antibiotic resistance,” said Blakely. “However, in more complex organisms, MBD has been repurposed to digest many other molecules. So, we suspected that drugs targeting human MBD-containing proteins would likely have non-microbial effects, perhaps even medically relevant ones.”

Indeed, prior to the Blakely lab identifying swip-10, scientists studying addiction were learning that the beta-lactam antibiotic ceftriaxone could diminish several brain changes that arise with chronic use of addictive drugs. What they didn’t know was what protein ceftriaxone bound to in the brain. In 2018, the Blakely lab reported that the protein made by the MBLAC1 gene is a major, if not exclusive, target for ceftriaxone. More recent data from mice engineered to eliminate MBLAC1 protein expression demonstrate a requirement for the protein in the ability of cocaine to establish long-term behavioral changes that reflect brain alterations scientists believe contributes to the drug’s abuse liability.

Remarkably, the Blakely lab has discovered that loss of swip-10 also causes age-dependent neurodegeneration.

“We think these findings link to recent studies implicating MBLAC1 as a contributor to risk for certain forms of Alzheimer’s disease as well as the ability of ceftriaxone to display neuroprotection in animal models,” said Hahn, co-inventor on the patent and a research associate professor of biomedical science in FAU’s Schmidt College of Medicine. “We are very excited that what began as a simple genetic screen using worms may be leading us to insights into a number of different brain disorders.”

- FAU -

About Florida Atlantic University:
Florida Atlantic University, established in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, the University serves more than 30,000 undergraduate and graduate students across six campuses located along the southeast Florida coast. In recent years, the University has doubled its research expenditures and outpaced its peers in student achievement rates. Through the coexistence of access and excellence, FAU embodies an innovative model where traditional achievement gaps vanish. FAU is designated a Hispanic-serving institution, ranked as a top public university by U.S. News & World Report and a High Research Activity institution by the Carnegie Foundation for the Advancement of Teaching. For more information, visit www.fau.edu.

Sahmyook University researchers identify genes associated with addiction to psychostimulant drugs

Researchers discover correlation between methamphetamine-induced behavior and the expression of specific genes in mice models lacking Period 2 gene

Peer-Reviewed Publication

SAHMYOOK UNIVERSITY

 

IMAGE: A TEAM OF RESEARCHERS FROM SAHMYOOK UNIVERSITY DISCOVERED THAT MICE LACKING PERIOD 2 (PER 2), A GENE ASSOCIATED WITH CIRCADIAN RHYTHM, SHOW GREATER ADDICTIVE RESPONSES TO THE PSYCHOSTIMULANT METHAMPHETAMINE BUT NOT COCAINE, POINTING AT THE ROLE OF PER2 EXPRESSION IN GOVERNING AN INDIVIDUAL’S VULNERABILITY TO DRUG ABUSE. view more 

CREDIT: HEE JIN KIM FROM SAHMYOOK UNIVERSITY, KOREA

Psychostimulant drugs like methamphetamine (METH) and cocaine (COC) affect the brain and nervous system by boosting alertness, attention, and energy levels of the individual. However, their persistent use results in drug addiction, compromising the life of the individual and burdening the healthcare, social, and legal systems as a consequence. In order to develop effective prevention and treatment strategies for drug addiction, it is critical to explore how these drugs interact with the nervous system and understand the mechanism underlying the addictive responses of individuals towards psychostimulants.

 

Interestingly, the gene Period 2 (Per2) has been linked with an increased tendency towards drug abuse. Per2 is associated with our circadian rhythms, our internal clock which regulates our sleep-wake cycle. Previous studies have reported that Per2 knockout (KO) mice, i.e., mice lacking the Per2 gene, show greater addictive responses and withdrawal symptoms towards METH compared to mice with normally functioning or overactive Per2. Accordingly, Per2 KO mice have been suggested as a potential animal model for understanding the molecular mechanisms underlying susceptibility towards drug abuse. However, its addictive responses to METH and other psychostimulant drugs like cocaine have not been examined as yet.

 

In order to bridge this gap, a group of researchers from Korea and Germany, led by Assistant Professor Hee Jin Kim from Sahmyook University compared how Per2 KO mice and wild-type (WT) mice, i.e., mice with Per2, responded to repeated self-administered doses of METH and COC. Their findings, made available online on 2 May 2023, were published in Volume 126 of the Journal Progress in Neuropsychopharmacology & Biological Psychiatry on 30 August 2023.

 

The researchers first investigated the motivational effect of these drugs and their impact on the locomotor activity of the mice using specialized tests. They noted that Per2 KO mice showed a stronger addictive response to METH when compared to the WT mice. However, when it came to drugs like COC, both groups of mice responded in a similar manner. Highlighting the importance of this observation, Dr. Kim exclaims, “The higher sensitivity of Per2 KO mice to METH rather than COC helped us deduce that different genetic factors were at play behind vulnerability to different drugs.”

 

Probing further, the researchers used a technique that identifies the coding sequence of an RNA–RNA sequencing–to pin down the genes involved in these addictive responses. They identified 19 genes that were only activated in response to repeated doses of METH but not COC. Using existing data, the researchers could correlate these genes with those that are activated in the region of the brain that responds to drug addiction.

 

Finally, to identify if any of the genes expressed due to METH exposure corresponded with METH-induced behavior, the researchers correlated the mRNA expression levels with the locomotor activity tests in Per2 KO and WT mice. They found that two specific genes, Arc and Junb, were expressed only in Per2 KO mice on METH exposure.

 

Highlighting their study’s findings, Dr. Kim says, “Our findings indicate that Arc and Junb, along with Per2, could be used as markers for susceptibility to METH abuse. If we are able to confirm the role of Arc and Junb expression in vulnerability to drug abuse, they could even be considered as potential targets for treating or preventing drug abuse.”

 

In summary, by unraveling the genetic factors that influence how our brains respond to psychostimulant drugs like METH and COC, researchers can pave the way for more targeted and personalized approaches to tackling drug abuse. In this regard, this study could open doors to the development of more effective diagnostic, preventive and treatment strategies, and potentially save countless lives.

 

***

 

Reference

DOI: https://doi.org/10.1016/j.pnpbp.2023.110782

 

 

About Sahmyook University

Sahmyook University is situated at Seoul, Republic of Korea. It has a long history rooted in educational philosophy of cultivating intellectually, spiritually, and physically holistic beings. It hinges on a balance between innovation, global outreach and community service. SU’s ultimate goal is to transform students into agents of love and truth that make the world a better place. It has chalked out a detailed road map to effectively achieve this goal: first, become a leading university in the Seoul Metropolitan Area by 2020 and, second, becoming an internationally leading university in our own specialty areas.

Website: https://www.syu.ac.kr/eng/

 

About the author

Prof. Hee Jin Kim is an Associate Professor of Uimyung Research Institute for Neuroscience, School of Pharmacy at Sahmyook University, Korea. She received her PhD in Pharmacology from Sahmyook University in 2010. Her research group at Sahmyook University is participating in developing evaluation methods for drug dependency along with diagnostics for neurodegenerative diseases, including autism spectrum disorder.

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JOURNAL

Progress in Neuro-Psychopharmacology and Biological Psychiatry

DOI

10.1016/j.pnpbp.2023.110782 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

The differential vulnerabilities of Per2 knockout mice to the addictive properties of methamphetamine and cocaine

GEOENGINEERING OR BREAK OUT THE UMBRELLAS

Shading the Great Barrier Reef from the sun might slow bleaching-induced coral decline

Shading corals for only a few hours a day during intense sunlight reduces bleaching in some species, scientists found, advancing the development of cooling and shading interventions to protect reefs

Peer-Reviewed Publication

FRONTIERS

Over the past two decades, coral reefs have declined at unprecedented rates. This is in part because of extreme weather events, which cause wide-spread coral bleaching, a process during which corals lose their color because of stressors, including changes in water temperature, light, or nutrient availability. One of the worst mass bleaching events occurred in 2016 and 2017 on the Great Barrier Reef, causing bleaching on 91% of the system’s reefs.

As frequency and severity of mass bleaching events are expected to increase in the future, researchers are looking for ways to protect corals from excessive radiation and temperatures. As part of the Cooling and Shading subprogram of the Reef Restoration and Adaptation Program (RRAP), which is developing solutions to help coral reefs resist, adapt to, and recover from warming ocean temperatures, researchers in Australia have examined the effectiveness of shading on two coral species.

“We show that intermittent shading under controlled conditions can moderate light stress and slow bleaching,” said Dr Peter Butcherine, a research fellow at Southern Cross University and lead author of the study published in Frontiers in Marine Science. “Reducing sunlight by 30% for four hours around solar noon can slow the onset of the bleaching response in some thermally-stressed shallow corals.”

Just four hours of shade slows bleaching

Researchers collected two species of stony corals, Turbinaria reniformis, commonly known as yellow scroll coral, and Duncanopsammia axifuga, also called whisker coral. After transportation and acclimatization to a lab, tanks containing coral fragments were covered with 30% shade cloth for either four hours around noon, or 24 hours. Shading corals for four hours in the middle of the day recreates light reductions similar to those on a cloudy day.

Results showed that shaded corals bleached significantly less than unshaded ones, and corals that were shaded for 24 hours bleached less than those shaded for four hours. Higher water temperatures also favored bleaching. 

Shading delayed the corals’ bleaching response by up to three degree heating weeks (DHW). Corals begin to accrue DHW once water temperature exceeds the maximum monthly mean water temperature by more than 1°C. After surpassing this threshold, they start to bleach. When heat stress reaches four DHW, significant coral bleaching can be observed.

Different responses to shading

Corals, however, did not respond in the same way to shading. For T. reniformis 30% shading for four hours a day was found enough to delay bleaching. The shading response of D. axifuga, however, was more limited: While the coral responded to 24-hour shading until three DHW, it became unresponsive after.

“The complex nature of coral interactions with their environment means there are likely to be a range of responses to shading. We showed that coral species can respond differently when shaded, but these differences were not necessarily detrimental, just different from each other,” Butcherine explained.

Yet, no matter how well corals respond to shading, thermal stress in intense prolonged marine heatwaves can still overwhelm the shading benefit, the researchers pointed out.

How to shade a reef

“This work directly informs the development of cooling and shading interventions to help protect the Great Barrier Reef during future bleaching events,” said Dr Daniel Harrison, a researcher at Southern Cross University and program lead of RRAP Cooling and Shading. “Coral reefs are a critically important ecosystem so it is vital to investigate all the possible ways we can help them survive climate change.”

There are several ways to shade reefs, including the use of artificial coverings and seawater fogging systems. The latter is one of the interventions that researchers in the RRAP Cooling and Shading program are working on. “The focus of the fogging technologies we are developing is for deployment at an individual reef site of some tens of hectares in size,” Harrison continued. Currently, the team’s efforts are aimed at localized cooling and shading of small high-value reef environments.

“Our trials show some promising results, but there is still more research and development required before the current technologies are ready for scaled up deployment in the field,” Harrison concluded.

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JOURNAL

Frontiers in Marine Science

DOI

10.3389/fmars.2023.1162896 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Intermittent shading can moderate coral bleaching on shallow reefs

ARTICLE PUBLICATION DATE

20-Sep-2023

COI STATEMENT

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.