When food shopping, I tend to opt for organic products. These often have an extra label touting their GMO-free status, since organic farming prohibits the use of genetically modified organisms. That includes organisms created with “new genomic techniques” (NGTs) like CRISPR. But there’s a paradox: plants bred using conventional mutagenesis (i.e., random mutagenesis with chemicals and radiation) are generally allowed in organic farming, even though these techniques are more likely than modern gene editing to produce unintended mutations in the final product.

NGTs allow for precise and targeted changes that could, in theory, occur naturally. The technology is moving fast; for example, base editing and prime editing (techniques derived from CRISPR technology) enable precise changes without cutting both strands of the DNA and come with even lower risk of unintended mutations. Both techniques have been in the news recently because of their therapeutic use: on May 15, we learned that base editing was used for the first personalized CRISPR therapy, while on May 19, it was announced that prime editing has been used to treat a person for the first time. Going back to plants, base and prime editing have been successfully applied in several important cereal crops (e.g., rice, wheat, maize) but not yet in sorghum. A recent preprint reported a high-efficiency genome editing toolkit for sorghum, paving the way for use of base and prime editing in this important crop. The authors conclude: “These advancements provide a streamlined approach to generating diverse genetic variation, facilitating crop improvement efforts that address food security challenges and contribute to carbon capture initiatives that are addressing climate change.”

This year, the EU is set to relax strict regulation of NGT plants (which are currently treated like GMO plants containing foreign DNA), marking a long-awaited and scientifically-supported shift in focus away from the breeding method and towards the characteristics of the final product. However, the paradox persists: NGT plants will still be excluded from organic farming, while those bred using conventional mutagenesis can stay.

High-frequency Wus2-integrated transformation toolkit enhances Cas9 editing efficiency and expands capability with SpRY in sorghum
In bioRxiv, 24 January 2025
From the group of Peggy Lemaux in the Department of Plant and Microbial Biology, University of California, Berkeley.

Snippet by Katrina Woolcock

Image credit: Figure 1 from Kantor et al., International Journal of Molecular Sciences, 2020 (CC BY)

Chronic stress is not just unpleasant; it degrades human health in several ways. One effect of chronic stress is increased susceptibility to depression, which itself exerts damaging effects on health and wellbeing. Neither of these conditions is deeply understood, and so perhaps it is unsurprising that the link between chronic stress and depression is unclear.

A recent paper in Nature provides interesting and useful clues to that link, in a set of experiments that journey from effects of antidepressants to basics of neuronal cell biology. The connection is in the machinery of autophagy (literally “self eating”) in which parts of a cell are digested in a recycling and reclamation process. The authors show that autophagy is central to stress and depression, specifically in neurons of an emotion-related brain region (the lateral habenula, or LHb). They find that acute stress activates autophagy in that region, but chronic stress (a model of depression in mice) does the opposite. Consistent with that fact, they show that autophagy in the LHb underlies antidepressant effects of various drugs, from antidepressant drugs themselves to metabolic inhibitors that (interestingly) also exert antidepressant actions. They then show that genetically inactivating autophagy—specifically in the LHb—causes depression-like effects. After several additional great experiments, the authors conclude: “our study proposes a fascinating possibility that LHb autophagy serves as a new cellular target of rapid antidepressants.”

Basic research by hard-working scientists all over the world is steadily eroding the power of scourges like depression.

Stress dynamically modulates neuronal autophagy to gate depression onset
In Nature, 9 April 2025
From the groups of Yihui Cui and Xiangnan Zhang at Zhejiang University.

Snippet by Stephen Matheson

Image credit: Extended data Figure 15 from Yang et al. cited above (CC BY-NC-ND)

I am regularly awestruck by the feats accomplished by our fellow animals. Here’s one that might not seem particularly praiseworthy: eating your body weight in a single meal. This is regularly achieved by ticks, and that’s a second reason you might want to stop reading, but hear me out. A tick gorges itself on blood (perhaps yours) until it has ballooned to at least ONE HUNDRED TIMES its pre-meal body weight. How is this even possible? Specifically, how does this animal’s gut accommodate the vast expansion that results from a blood feast?

A new paper in Cell Reports asked that question, focusing on the muscles of the tick’s gut. The authors looked at two interesting consequences of feeding in the gut: proliferation of gut stem cells, and fission (splitting) of mitochondria. Stem cell proliferation seems a reasonable path toward the necessary expansion of the gut, but when the authors inhibited that process, ticks happily gorged themselves to the same extent. But inhibition of mitochondrial fission disrupts feeding, and the authors show why: more mitochondria are needed for ATP, which is needed for upregulation of a muscle protein called troponin T (delightfully abbreviated TNT). Experimental reduction of TNT expression inhibits muscle function, and ruins the tick’s meal. Sad.

Mitochondrial fission regulates midgut muscle assembly and tick feeding capacity
In Cell Reports, 22 April 2025
From the group of Jingwen Wang at Fudan University

Snippet by Stephen Matheson

Image credit: graphical abstract from Zhong et al. (CC BY-NC)

Autism is extremely heterogeneous. It is shaped by a complex interplay of genetic and environmental factors, which have been studied for decades, making RFK Jr’s pledge to determine “what has caused the autism epidemic” by September highly questionable. Some worry that the effort will be biased towards vaccine-autism theories, which have been repeatedly and thoroughly debunked. The strongest known contributors to autism risk are genetic, but there is reasonable evidence that environmental factors during pregnancy can affect autism risk in offspring (and, of course, these factors may interact with genetic predispositions). For example, activation of the mother’s immune system during pregnancy has been linked to increased autism risk. Proving causation in humans is tricky, so much of the evidence on this “maternal immune activation” comes from animal models. A recent preprint sheds light on the potential molecular mechanisms, suggesting that changes in DNA methylation disrupt neural circuit formation in the offspring of mice treated with a viral mimetic (poly(I:C), or PIC) during pregnancy.

The authors are careful to make the distinction between the immune activation in their experiments and the immune activation occurring upon mild infection or vaccination: “The cytokine levels post-PIC injection are comparable to those produced during a cytokine storm due to influenza or other serious infections. Such levels of proinflammatory cytokines are not produced during common cold infections or after immunizations.” So, if anything, vaccines before and during pregnancy might reduce autism risk by protecting against serious infections.

Maternal Immune Activation Disrupts Epigenomic and Functional Maturation of Cortical Excitatory Neurons
In bioRxiv, 29 April 2025
From the groups of Margarita Behrens, Eran Mukamel, and Joseph Ecker

Snippet by Katrina Woolcock

Image credit: Figure 1 from Lai et al. linked above (CC-BY-NC-ND)

Last month, the UK Supreme Court ruled that the legal definition of a woman is based on biological sex. Snippets are not the place for discussing legal rulings and their ramifications, but I want to focus on one quote from the decision: “the concept of sex is binary, a person is either a woman or a man”. Such simplicity might be convenient in terms of legal clarity but is at odds with the reality of human biology. Biological sex is by no means strictly binary: for example, intersex people are born with physical sex characteristics that do not fit typical definitions of male or female. A vast array of “differences in sex development” (DSDs) often underlie such variation, with much remaining to be discovered about the biological mechanisms. A recent preprint from the Institut Pasteur in France sheds light on a DSD called 46,XY sex-reversal, whereby an individual with male chromosomes develops female genitalia and reproductive structures. DHX37, a gene encoding an RNA helicase, is one of several genes implicated in 46,XY sex-reversal. Among other experiments, the authors analyzed RNA transcripts physically interacting with wild-type and mutant DHX37 proteins, providing insights into how DHX37 mutations might disrupt early testicular development. Such studies will help unravel the vast natural variation in sex development, hopefully changing oversimplified ‘either/or’ views of sex.

Altered RNA-processing provides a mechanistic framework delineating human sex-reversal associated with pathogenic variants in the RNA-helicase DHX37
In bioRxiv, 13 January 2025
From the group of Anu Bashamboo

Snippet by Katrina Woolcock

Image credit: Figure 4A-4D from Elzaiat et al. linked above (CC-BY)

mRNA vaccines have been administered billions of times worldwide and their importance was underscored by the 2023 Nobel Prize in Physiology or Medicine, awarded to Katalin Karikó and Drew Weissman “for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19”. Nonetheless, mRNA vaccines have been the subject of controversy, some of it rooted in misinformation. For example, false claims and conspiracy theories about mRNA vaccines altering DNA gained traction, spreading fear of long-term consequences. Far from it, mRNA does not enter the nucleus and, even if it did, would not be able to interact with or change DNA. In fact, mRNA is highly unstable, making the effectiveness of mRNA vaccines rather surprising. A recent paper in Nature helps explain how the vaccine mRNAs manage to stick around long enough to produce the protein needed for an immune response. The authors found that an enzyme called TENT5A extends the mRNA poly(A) tails, which are crucial for mRNA stability and translation. The findings will aid the design of future mRNA therapeutics, which are under investigation for treating a range of diseases, from flu to cancer. The authors are particularly proud that the paper is exclusively a product of Polish institutions; yet the path to publication wasn’t easy – it took more than two years and multiple rounds of revision before their manuscript was accepted.

Re-adenylation by TENT5A enhances efficacy of SARS-CoV-2 mRNA vaccines
In Nature, 16 April 2025
From the groups of Andrzej Dziembowski and Seweryn Mroczek, International Institute of Molecular and Cell Biology and University of Warsaw

Snippet by Katrina Woolcock

Image credit: Figure 3 from Krawczyk et al. linked above (CC-BY)

My experience of human pregnancy, while vicarious, has long associated pregnancy with uncomfortable body heat. This is both interesting and worrying to me, and so I was curious to read this new paper in Cell Reports: “Prolactin modulation of thermoregulatory circuits provides resilience to thermal challenge of pregnancy.” The title grabbed me (as a good title should), especially the phrase “resilience to thermal challenge of pregnancy.” I know that body temperature increases in early pregnancy, and I assumed it stays that way. But no. Here is how the authors frame their question in the Introduction:

A mother must lose this extra metabolic heat both for herself and for her developing offspring. Despite these thermal challenges, core body temperature actually decreases in late pregnancy, suggesting that there are adaptive changes in thermoregulation to promote heat loss and to ultimately provide a safe environment for fetal development.

Prolactin, a major hormone of pregnancy, is thought to control this adaptive action by acting peripherally. In a series of manipulations of prolactin receptor function in the hypothalamus, the authors provide evidence that a major site of prolactin’s action, in thermal regulation during pregnancy, is in the brain. The authors conclude that “prolactin has a key role in regulating the thermoregulatory circuits, providing optimal conditions for successful pregnancy.”

Prolactin modulation of thermoregulatory circuits provides resilience to thermal challenge of pregnancy
In Cell Reports, 22 April 2025
From the groups of Sharon Ladyman and Rosemary S.E. Brown

Snippet by Stephen Matheson

Image credit: Graphical abstract from Ladyman et al. linked above (CC-BY-NC)