“Soft” CRISPR May Offer a New Fix for Genetic Defects

Restorative gene editing using sequences from the counterpart chromosome: The standard CRISPR enzyme Cas9 offers the ability to make repairs but also potentially results in unintended mutations (mutagenic events) at the targeted site and possibly elsewhere in the genome (left). In contrast, the nickase enzyme results in more efficient gene correction and no mutagenic events (right).
Source: University of California San Diego

Curing debilitating genetic diseases is one of the great challenges of modern medicine. During the past decade, development of CRISPR technologies and advancements in genetics research brought new hope for patients and their families, although the safety of these new methods is still of significant concern.

Publishing July 1 in the journal Science Advances, a team of biologists at the University of California San Diego that includes postdoctoral scholar Sitara Roy, specialist Annabel Guichard and Professor Ethan Bier describes a new, safer approach that may correct genetic defects in the future. Their strategy, which makes use of natural DNA repair machinery, provides a foundation for novel gene therapy strategies with the potential to cure a large spectrum of genetic diseases.

In many cases, those suffering from genetic disorders carry distinct mutations in the two copies of genes inherited from their parents. This means that often, a mutation on one chromosome will have a functional sequence counterpart on the other chromosome. The researchers employed CRISPR genetic editing tools to exploit this fact.

“The healthy variant can be used by the cell’s repair machinery to correct the defective mutation after cutting the mutant DNA,” said Guichard, the senior author of the study, “Remarkably, this can be achieved even more efficiently by a simple harmless nick.”

Mining's effect on fish warrants better science-based policies

Migrating sockeye salmon approach their spawning grounds on a tributary of the Copper River.
Credit: University of Alaska Fairbanks

A new paper published in Science Advances synthesizes the impact of metal and coal mines on salmon and trout in northwestern North America, and highlights the need for more complete and transparent science to inform mining policy.

It is the first comprehensive effort by an interdisciplinary group of experts that explicitly links mining policy to current understanding of watershed ecology and salmonid biology.

“Our paper is not for or against mining, but it does describe current environmental challenges and gaps in the application of science to mining governance. We believe it will provide critically needed scientific clarity for this controversial topic,” said lead author Chris Sergeant, a graduate student at the University of Alaska Fairbanks College of Fisheries and Ocean Sciences and a research scientist at the University of Montana.

For the study, experts integrated and reviewed information on hydrology, river ecology, aquatic toxicology, biology and mining policy. Their robust assessment maps more than 3,600 mines throughout Montana, Washington, British Columbia, the Yukon and Alaska. The size of the mines ranges from family-run placer sites to massive open-pit projects.

Biomedical engineering students work on transgender health project

UC College of Engineering and Applied Science students Anna King, left, and Rucha Tadwalkar use 3D printers in a biomedical engineering lab.
Photo/Michael Miller

Biomedical engineering students at the University of Cincinnati created a product to help decrease the gender dysphoria experienced by some transgender men during menstruation prior to gender-confirmation surgery.

UC College of Engineering and Applied Science students Rucha Tadwalkar and Anna King wanted to help people suffering from gender dysphoria, the condition of feeling one's emotional and psychological identity to be at variance with one's birth sex.

The students spoke to experts in adolescent and transition medicine at the Transgender Health Clinic at Cincinnati Children’s Hospital Medical Center.

“Our goal was to create a menstrual device that is inclusive of all individuals to decrease the mental health side effects of gender dysphoria, which are heightened during the menstrual cycle” Tadwalkar said.

One in 250 adults representing about 1 million people in the United States identify as transgender, according to the National Institutes of Health.

New study allows researchers to more efficiently form human heart cells from stem cells

Jianhua Zhang, PhD, Senior Scientist
Credit: Clint Thayer

Lab-grown human heart cells provide a powerful tool to understand and potentially treat heart disease. However, the methods to produce human heart cells from pluripotent stem cells are not optimal. Fortunately, a new study out of the University of Wisconsin–Madison Stem Cell & Regenerative Medicine Center is providing key insight that will aid researchers in growing cardiac cells from stem cells.

The research, published recently in eLife, investigates the role of extracellular matrix (ECM) proteins in the generation of heart cells derived from human pluripotent stem cells (hPSCs). The ECM fills the space between cells, providing structural support and regulating formation of tissues and organs. With a better understanding of ECM and its impact on heart development, researchers will be able to more effectively develop heart muscle cells, called cardiomyocytes, that could be useful for cardiac repair, regeneration and cell therapy.

“How the ECM impacts the generation of hPSC-cardiomyocytes has been largely overlooked,” says Jianhua Zhang, a senior scientist at the Stem Cell and Regenerative Medicine Center. “The better we understand how the soluble factors as well as the ECM proteins work in the cell culture and differentiation, the closer we get to our goals.”

Researchers like Zhang have been looking to improve the differentiation of hPSCs into cardiomyocytes, or the ability to take hPSCs, which can self-renew indefinitely in culture while maintaining the ability to become almost any cell type in the human body and turn them into heart muscle cells. To investigate the role of the ECM in promoting this cardiac differentiation of hPSCs, Zhang tested a variety of proteins to see how they impacted stem cell growth and differentiation — specifically, ECM proteins including laminin-111, laminin-521, fibronectin and collagen.

The evolutionary relationships of two groups of ancient invertebrates revealed

A scanning electron microscopy image of a Kamptozoa, a small aquatic invertebrate.
Credit: Dr. Natalia Shunatova / OIST

Kamptozoa and Bryozoa are two phyla of small aquatic invertebrates. They are related to snails and clams (collectively called mollusks), bristleworms, earthworms, and leeches (collectively called annelids), and ribbon worms (nemertea). But their precise position on the tree of life, and how closely related they are to these other animals, has always puzzled evolutionary biologists. Previous studies have consistently moved them around. What’s more, while Kamptozoa and Bryozoa were originally considered to form one group, they were separated based on their appearance and anatomy. Now, by using cutting-edge sequencing technology and powerful computational analysis, scientists from the Okinawa Institute of Science and Technology Graduate University (OIST), in collaboration with colleagues from St-Petersburg University and Tsukuba University, have revealed that the two phyla split from mollusks and worms earlier than previous studies have suggested, and thus they indeed form a distinct group.

A Souped-Up Gene Promoter Stops Heat from Sapping Plant Defenses

The immune system of plants relies on the hormone salicylic acid, which helps fine-tune their defenses against infections and insect infestations. But at warm temperatures, plants turn off their salicylic acid production. New research from HHMI Investigators reveals why and uses genetic engineering to boost immune function during warm spells.
Credit: Lesley Warren Design Group, ON, Canada

Plants’ immune defenses falter during heat waves, rendering them more vulnerable to insects and pathogens under climate change. HHMI scientists have now figured out why high temperatures knock out a key defense system and they’ve come up with a strategy that bolsters plant immunity.

Plants feeling the heat face risks beyond wilting. During heat waves, plants’ defenses falter, rendering them more vulnerable to infection and infestation. This is especially worrisome as climate change is making heat waves more frequent and intense.

Sheng Yang He
Duke University
Plant Sciences Microbiology

“Plants actually have a very powerful innate immune system that explains why they’ve survived so long on Earth,” says plant scientist Sheng Yang He, who is a Howard Hughes Medical Institute (HHMI) Investigator at Duke University. “But now we know that this immune system may not function so well in a hot climate, especially for many cool-weather crops. Continued warming of the climate may exacerbate this reduction of innate immunity and increase diseases and insect infestations in the future.”

He’s team has unearthed new clues to why heat saps plants’ immunity. That allowed them to find a genetic solution to keep a key plant defense system online during warm spells, the researchers report June 29, 2022, in Nature.

Plants’ immune function requires the hormone salicylic acid, which helps coordinate which defenses plants raise or lower. But sweltering plants throttle back on their production of salicylic acid, and researchers haven’t known why.

Home Sweet Home: A Study of the ‘Chemical Soup’ in our Houses

Chances are very good that as you read this, you are seated somewhere indoors. The surfaces around you are covered in microbes and you are also covered in microbes. All those microbes are busy excreting molecules and responding to the rest of the molecules in the mix. What does all of this mean for your health?

“We are living in a soup of chemistry,” says UConn Department of Chemistry researcher Alexander Aksenov, who is working to understand this microbial and molecular soup in our indoor environments and how it could be impacting our health. He and a multidisciplinary team of researchers, including from the University of California, San Diego, Colorado State University, and the University of Colorado published a paper today in Science Advances exploring these under-studied questions, with some surprising findings that could help inform us how to live healthier lives indoors.

Accounting for our full day, including time spent in cars, on average we spend over 90% of our time indoors, says Aksenov, so the indoor environment is by far the most important for us.

Previous studies show human activities impact our indoor environments, through things like gas stoves, chemical off-gassing, and the type of cleaning solutions we use. These studies usually looked at a limited number of molecules. For this study, the researchers sought to explore the full suite of molecules and microbes within a household environment.

Tonga volcano eruption triggered atmospheric gravity waves that reached the edge of space

Hunga Tonga-Hunga Ha‘apai erupts
Credit: NASA Visible Earth

The eruption of Hunga Tonga-Hunga Ha’apai on 15 January 2022 created waves that reverberated around the earth and reached 100km into the ionosphere.

The eruption of the Hunga Tonga-Hunga Ha’apai submarine volcano in January 2022 was one of the most explosive volcanic events of the modern era, a new study has confirmed.

A multi-institutional international team of researchers combined extensive satellite data with ground-level observations to show that the eruption was unique in observed science in both its magnitude and speed, and in the range of the fast-moving gravity and atmospheric waves it created.

Following a series of smaller volcanic events beginning in December 2021, Hunga Tonga erupted on 15 January this year, producing a vertical plume that extended more than 50km above the Earth’s surface.

The heat released from the water and hot ash in the plume was the most significant source of gravity waves on Earth for the following 12 hours. The eruption produced ripple-like gravity waves that satellite observations show extended across the Pacific basin.

Co-author Dr Scott Osprey, Department of Physics, University of Oxford advised that there could be further impacts from the Hunga Tonga eruption:

Thin crust or thick?

Photo credit: Erik Christensen.
Licensed under the Creative Commons Attribution-Share Alike 3.0 Unported,

The crusty conundrum carries fundamental implications. The thickness of continental crust — the part of Earth’s crust that forms land masses and continents — plays an important role in everything from the gradual movement of continents to the evolution of animal species on land and in shallow waters along coastlines.

The Earth is covered by two kinds of crust — continental and oceanic. The thinner oceanic crust is normally a little more than four miles thick, while the thicker continental crust is often as much as 25 miles thick. Continental crust is also much less dense than its oceanic counterpart.

In 1962, famed Princeton geologist Harry Hess theorized that the thickness of continental crust had to do with sea level and ocean depth. Deeper oceans enabled the formation of thicker continental crust, Hess posited. But as the crust thickens and rises above sea level, Hess said, erosion gradually starts to break it down.

The Hess theory proved quite durable, remaining unchallenged for decades. But in the past five years, new theories about oceans and land formation in the ancient world began to raise questions. For example, the geochemical signatures of ancient sediments around the world suggest to many researchers that during Earth’s Archean eon, which lasted from 4,000 million years ago until 2,500 million years ago, Earth was a “water world.” The planet was covered by deep oceans, with no continents rising above the water’s surface.

Researchers discover new leukemia-killing compounds

Natasha Kirienko (left) and Svetlana Panina in Kirienko’s Rice University laboratory in 2019. Kirienko, associate professor of biosciences, and Panina, a former postdoctoral research associate in Kirienko’s lab, collaborated with researchers at the University of Texas MD Anderson Cancer Center to study potential new mitophagy-inducing drugs that could be paired with other chemotherapies to deliver a potent one-two punch to leukemia.
Photo by Jeff Fitlow/Rice University

Researchers from Rice University and the University of Texas MD Anderson Cancer Center have discovered potential new drugs that work in concert with other drugs to deliver a deadly one-two punch to leukemia.

The potential drugs are still years away from being tested in cancer patients, but a recently published study in the journal Leukemia highlights their promise and the innovative methods that led to their discovery.

In previous studies, the research groups of Rice biochemist Natasha Kirienko and MD Anderson physician-scientist Marina Konopleva screened some 45,000 small-molecule compounds to find a few that targeted mitochondria. In the new study, they chose eight of the most promising compounds, identified between five and 30 closely related analogs for each and conducted tens of thousands of tests to systematically determine how toxic each analog was to leukemia cells, both when administered individually or in combination with existing chemotherapy drugs like doxorubicin.

“One of the big challenges was to establish optimal conditions and doses for testing on both cancer cells and healthy cells,” said study lead author Svetlana Panina , a researcher at the University of Texas at Austin who conducted the research during her postdoctoral studies at Rice. “The results from our previously published cytotoxicity assay were helpful, but very little is known about these small-molecule compounds. None of them had been thoroughly described in other studies, and we had to essentially start from scratch to determine how much to use, what they do in cells, everything. All the doses and treatment conditions had to be adjusted by multiple preliminary experiments.”