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Koo and his team tested CREME on another AI-powered DNN genome analysis tool called Enformer. They wanted to know how Enformer’s algorithm makes predictions about the genome. Koo says questions like that are central to his work.

“We have these big, powerful models,” Koo said. “They’re quite compelling at taking DNA sequences and predicting gene expression. But we don’t really have any good ways of trying to understand what these models are learning. Presumably, they’re making accurate predictions because they’ve learned a lot of the rules about gene regulation, but we don’t actually know what their predictions are based off of.”

With CREME, Koo’s team uncovered a series of genetic rules that Enformer learned while analyzing the genome. That insight may one day prove invaluable for drug discovery. The investigators stated, “CREME provides a powerful toolkit for translating the predictions of genomic DNNs into mechanistic insights of gene regulation … Applying CREME to Enformer, a state-of-the-art DNN, we identify cis-regulatory elements that enhance or silence gene expression and characterize their complex interactions.” Koo added, “Understanding the rules of gene regulation gives you more options for tuning gene expression levels in precise and predictable ways.”

Summary: Researchers found that mutations in the Sox3 gene cause hypopituitarism, a condition where the pituitary gland produces insufficient hormones, leading to growth issues and infertility. In a study on mice, they discovered that Sox3 mutations affect brain cells called NG2 glia, which are essential for hormone production.

Treating the mice with aspirin or altering their gut microbiome restored NG2 glia levels and reversed hypopituitarism. These findings suggest that both aspirin and gut bacteria could be explored as potential treatments for people with Sox3 mutations or other hormone-related disorders.

Researchers have developed a groundbreaking system that uses bacteria to mimic the problem-solving capabilities of artificial neural networks.

Cell-based biocomputing is a novel technique that uses cellular processes to perform computations. Such micron-scale biocomputers could overcome many of the energy, cost and technological limitations of conventional microprocessor-based computers, but the technology is still very much in its infancy. One of the key challenges is the creation of cell-based systems that can solve complex computational problems.

Now a research team from the Saha Institute of Nuclear Physics in India has used genetically modified bacteria to create a cell-based biocomputer with problem-solving capabilities. The researchers created 14 engineered bacterial cells, each of which functioned as a modular and configurable system. They demonstrated that by mixing and matching appropriate modules, the resulting multicellular system could solve nine yes/no computational decision problems and one optimization problem.

Continue reading “Genetically engineered bacteria solve computational problems” »

Meet Barbara Di Ventura, an engineer turned synthetic biologist at the University of Freiburg, who explores protein dynamics across cell types. Outside of the laboratory, she moonlights as a musician. Di Ventura harmonizes her passion for art and science in musical abstracts, using a guitar to riff about her latest research, transforming scientific communication into a lively experience.

What inspired you to start creating musical abstracts?

I was inspired by Uri Alon, a systems biologist at the Weizmann Institute of Science, who played the guitar and sang songs about his group’s projects in an entertaining way. Then in 2021, we published a paper on a novel optogenetic tool for controlling gene expression in bacteria, and I had this vision to write a song about it.¹ We’re constantly asked to describe our work in new ways despite the numerous figures we produce. To me, writing song lyrics is easier than new text. The song “American Pie” came to mind, and it sounded cool with “Bye-bye, L-arabinose drive,” where L-arabinose is the normal inducer of this system.

In some mammals, the timing of the normally continuous embryonic development can be altered to improve the chances of survival for both the embryo and the mother. This mechanism to temporarily slow development, called embryonic diapause, often happens at the blastocyst stage, just before the embryo implants in the uterus.

During diapause, the embryo remains free-floating and pregnancy is extended. This dormant state can be maintained for weeks or months before development is resumed, when conditions are favorable. Although not all mammals use this reproductive strategy, the ability to pause development can be triggered experimentally. Whether human cells can respond to diapause triggers remained an open question.

Now, a study by the labs of Aydan Bulut-Karslıoğlu at the Max Planck Institute for Molecular Genetics in Berlin and Nicolas Rivron at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences in Vienna, has identified that the molecular mechanisms that control embryonic diapause also seem to be actionable in human cells.

“We are excited to explore the other trees by applying similar technologies.” first appeared on The Cool Down.

NEW YORK — In a groundbreaking development, scientists have created a revolutionary method to track the spread of cancer throughout the body, potentially paving the way for more effective treatments against this devastating disease. The new technology, developed by researchers at Cold Spring Harbor Laboratory and Weill Cornell Medicine in New York, uses genetic “barcodes” to monitor the movement of individual cancer cells, providing unprecedented insights into the process of metastasis.

In recent years, the scientific community has made significant strides in the field of gene editing, particularly through the development of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) systems. In 2020, the Nobel Prize in Chemistry was awarded to the scientists for the discovery of CRISPR–Cas9 system, a revolutionary genome editing technology that advanced DNA therapeutics. Subsequently, the CRISPR–Cas13 system has emerged as a potential tool to identify and rectify errors in RNA sequences. CRISPR–Cas13 is a novel technology is specifically engineered for virus detection and RNA-targeted therapeutics. The CRISPR RNA (CrRNA) targets specific and non-specific RNA sequences, and Cas13 is an effector protein that undergoes conformational changes and cleaves the target RNA. This RNA-targeting system holds tremendous promise for therapeutics and presents a revolutionary tool in the landscape of molecular biology.

Now, in a recently published BioDesign Research study, a team of researchers led by Professor Yuan Yao from ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, China has elucidated the latest research trends of CRISPR–Cas13 in RNA-targeted therapies. Talking about this paper, which was published online on 6 September 2024, in Volume 6 of the journal, Prof. Yao says, “By focusing on RNA-;the intermediary between DNA and proteins-;CRISPR-Cas13 allows scientists to temporarily manipulate gene expression without inducing permanent changes to the genome. This flexibility makes it a safer option in scenarios where genome stability is critical.”

RNA plays a central role in carrying genetic information from DNA to protein-synthesizing machinery, and also regulates gene expression and participates in numerous cellular processes. Defects in RNA splicing or mutations can lead to a wide variety of diseases, ranging from metabolic disorders to cancer. A point mutation occurs when a single nucleotide is erroneously inserted, deleted, or changed. CRISPR–Cas13 plays a role in identifying and correcting these mutations by employing REPAIR (RNA editing for programmable A-to-I replacement) and RESCUE (RNA editing for specific C-to-U exchange) mechanisms. Explaining the applications of Cas13-based gene editors, Prof. Yao adds, “The mxABE editor, for example, can be used to correct a nonsense mutation linked with Duchenne muscular dystrophy that can be corrected with mxABE. This approach has proved high editing efficiency, restoring dystrophin expression to levels more than 50% of those of the wild type.”

Imagine being one cartwheel away from changing your appearance. One flip, and your brunette locks are platinum blond. That’s not too far from what happens in some prokaryotes, or single-cell organisms, such as bacteria, that undergo something called inversions.

A study led by scientists at Stanford Medicine has shown that inversions, which cause a physical flip of a segment of DNA and change an organism’s genetic identity, can occur within a single gene, challenging a central dogma of biology — that one gene can code for only one protein.

“Bacteria are even cooler than I originally thought, and I’m a microbiologist, so I already thought they were pretty cool,” said Rachael Chanin, PhD, a postdoctoral scholar in hematology. Microbiologists have known for decades that bacteria can flip small sections of their DNA to activate or deactivate genes, Chanin said. To the team’s knowledge, however, those somersaulting pieces have never been found within the confines of a single gene.