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Category: genetics

Promoters and enhancers: Tool catches gene-controlling DNA sequences doing each other’s jobs

Researchers at the Weill Institute for Cell and Molecular Biology have uncovered new evidence that two major types of gene-controlling DNA sequences, promoters and enhancers, operate with a shared logic and often perform the same jobs. The finding, made possible through a high-throughput assay they developed called QUASARR-seq, could reshape how scientists design gene therapies, interpret disease-related mutations, and understand cancer genetics.

New research from the lab of Haiyuan Yu, Tisch University Professor of Computational Biology at Cornell University’s College of Agriculture and Life Sciences (CALS) and faculty at the Weill Institute, reveals that drawing a distinction between the two classes gene controllers may be too black and white—they seem to respond to the same biological rules and act in concert.

In a study published in Nature Communications on Jan. 30 and led by Mauricio Paramo, a graduate student at the Weill Institute, the team developed a technology capable of measuring an element’s promoter and enhancer activity simultaneously, in close collaboration with the lab of John Lis, Barbara McClintock Professor of Molecular Biology & Genetics. This is significant because, until now, most technologies could measure only one function at a time, leaving open the question of whether—and how—the two activities interact inside the same DNA sequence.

The Virtual Biotech: A Multi-Agent AI Framework for Therapeutic Discovery and Development

Drug discovery and development requires integrating diverse evidence across biological scales and data modalities. However, relevant data, tools, and expertise remain fragmented across teams and organizations, making integration difficult. To address these challenges, we introduce the Virtual Biotech, a coordinated team of AI agents that mirrors the structure of human therapeutic research organizations to support end-to-end computational discovery. The Virtual Biotech is led by a Chief Scientific Officer agent that receives scientific queries, delegates them to domain-specialized scientist agents, and integrates their outputs through data-driven reasoning. Scientist agents leverage complementary tools and knowledge sources spanning statistical genetics, functional genomics, pathways and interactions, chemoinformatics, disease biology, and clinical data. We showcase the Virtual Biotech across three translational applications. First, the agents autonomously annotated and analyzed outcomes from 55,984 clinical trials to identify genomic features of drug targets associated with trial success. More than 37,000 clinical-trialist agents curated structured trial outcomes and linked targets to multi-omic annotations, including cell-type-specific features derived by the agents from single-cell RNA-sequencing atlases. The agents discovered that drugs targeting cell-type-specific genes were 40% more likely to progress from Phase I to Phase II and 48% more likely to reach market (Phase IV), while exhibiting 32% lower adverse event rates. Second, the Virtual Biotech evaluated B7-H3 as a lung cancer target, integrating statistical genetics, single-cell, spatial, and clinicogenomic evidence to propose an antibody–drug conjugate strategy while identifying key liabilities and differentiation opportunities. Third, the platform analyzed a terminated ulcerative colitis trial targeting OSMR β to infer potential failure mechanisms and proposed biomarker-guided enrollment strategies to address precision-medicine gaps. Together, these results illustrate how the Virtual Biotech can enable more transparent, efficient, and comprehensive multi-scale therapeutic analyses, helping to accelerate early-stage drug discovery workflows while keeping human scientists in the loop.

The authors have declared no competing interest.

Balancing IL-17–mediated protection and IFN-γ–driven pathology at mucocutaneous barriers

Controlling mucocutaneous barriers by cytokines.

Impaired IL-17 leads to mucocutaneous bacterial and fungal infections, whereas enhanced IL-17 promotes psoriasis and periodontitis.

Interferon (IFN)-γ deficiency causes infections by intracellular pathogens, whereas exacerbated mucosal IFN-γ activity promotes oral candidiasis, even when IL-17 responses are intact.

JAK inhibition in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy remits oral candidiasis and multiorgan autoimmunity.

IFN-γ drives Candida auris skin infection by impairing the epithelial barrier. Excess IFN-γ, tumor necrosis factor, and types I/III IFN activities contribute to pathology during bacterial and protozoan skin infections and pulmonary viral, bacterial, mycobacterial, and fungal infections.

Although immune deficiency causes mucosal infection, epithelial disruption by immunopathology represents a novel and underappreciated mechanism of infection susceptibility at barrier sites. sciencenewshighlights ScienceMission https://sciencemission.com/Balancing-IL-17

Continue reading “Balancing IL-17–mediated protection and IFN-γ–driven pathology at mucocutaneous barriers” | >

Jumping DNA Sequences Drive Early Tumor Growth

New research reveals that LINE-1 retrotransposons don’t just nudge genes, they also trigger massive structural upheavals early in cancer development.

Read about the findings.

Where there’s a bountiful host, there are parasites ready to take advantage of the resources. This holds true even at microscopic levels. Lying within human DNA are repetitive elements called LINE-1 (L1) retrotransposons that promote their own propagation at the cost of the host organism’s health.1 These genetic parasites create copies of themselves that then get inserted at new locations within the genome. Until recently, scientists thought that the activity of L1s mostly resulted in local alterations to genes.

Now, in a new study published in Science, researchers have demonstrated that L1s can trigger dramatic structural changes in DNA, resulting in cancer-causing mutations.2 These findings, which shed light on the intricate relationship between cancer evolution and the genome, could lead to improved diagnostic and therapeutic strategies for different cancers.

“Cancer genomes are more influenced by these jumping fragments of DNA parasites than we previously thought,” said José Tubio, a molecular biologist at the University of Santiago de Compostela, in a statement.

Does suppression of HIV replication protect against severe M

tuberculosis infection?

Philana Ling Lin & team report on SIV/ART/TB models, finding antiretroviral treatment reduces pulmonary TB pathology, yet does not prevent extrapulmonary spread of TB.

1Department of Pediatrics, Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

2Center for Vaccine Research.

3Department of Microbiology and Molecular Genetics, and.

4Division of Laboratory Animal Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Continue reading “Does suppression of HIV replication protect against severe M” | >

Management of Inherited CNS Small Vessel Diseases: The CADASIL Example: A Scientific Statement From the American Heart Association

Lacunar infarcts and vascular dementia are important phenotypic characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the most common inherited cerebral small vessel disease. Individuals with the disease show variability in the nature and onset of symptoms and rates of progression, which are only partially explained by differences in pathogenic mutations in the NOTCH3 gene. Recognizing the disease early in its course and securing a molecular diagnosis are important clinical goals, despite the lack of proven disease-modifying treatments.

Abstract: Emily Gutierrez-Morton

Yanchang Wang and colleagues (Florida State University) show that in yeast, polo-like kinase Cdc5 promotes the phosphorylation of SUMO protease Ulp2, reducing its affinity for SUMO chains and thereby facilitating polySUMOylation.

Genetics CellCycle

1Infectious Diseases Division, Department of Medicine and.

2Division of Plastic and Reconstructive Surgery, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.

3Department of Mathematics, Dartmouth College, Hanover, New Hampshire, USA.

Immune cells selectively pull DNA from dying nuclei, revealing a process dubbed nucleocytosis

Over the years, cell biology has built a detailed picture of how cells compartmentalize their internal functions. Central to this organization is the nucleus, which houses the genetic material and is separated from the cytoplasm by a robust nuclear envelope.

Traditionally, the nuclear membrane has been considered a strict barrier, maintaining nuclear integrity except during carefully controlled processes such as mitosis. As a result, the release of nuclear material has largely been associated with cellular damage or death.

However, recent work by a research team in Japan suggests that this view may be incomplete.

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