Lead author Joseph Silk, a professor in the Department of Physics and Astronomy at Johns Hopkins University, explained that this discovery could change our understanding of how galaxies formed. We know these monster black holes exist at the center of galaxies near our Milky Way, but the big surprise now is that they were present at the beginning of the universe as well and were almost like building blocks or seeds for early galaxies.

The study, published in the Astrophysical Journal Letters, analyzed distant galaxies from the early universe observed through the Webb telescope. These galaxies appeared much brighter than expected and contained unusually high numbers of young stars and supermassive black holes.

The findings challenge the conventional idea that black holes formed after the collapse of supermassive stars and that galaxies formed after the first stars appeared. Instead, the analysis suggests that black holes and galaxies coexisted and influenced each other’s development during the first 100 million years of the universe.

Researchers from the University of Colorado Cancer Center have solved a cellular mystery that may lead to better therapies for colorectal and other types of cancer.

Peter Dempsey, Ph.D., professor of pediatrics– developmental biology in the CU School of Medicine, and Justin Brumbaugh, Ph.D., assistant professor of molecular, cellular, and developmental biology at CU Boulder, recently published a paper in the journal Nature Cell Biology showing the importance of the H3K36 methylation process in regulating plasticity and regeneration in intestinal cells.

“The intestine has an enormous ability to regenerate itself after injury, and it does this through a model of dedifferentiation,” Dempsey explains. “The cells dedifferentiate back into a type of regenerative stem cell after injury, and those stem cells eventually recover the intestine and turn back to normal cells.”

To identify host factors that affect Bovine Herpes Virus Type 1 (BoHV-1) infection we previously applied a genome wide CRISPR knockout screen targeting all bovine protein coding genes. By doing so we compiled a list of both pro-viral and anti-viral proteins involved in BoHV-1 replication. Here we provide further analysis of those that are potentially involved in viral entry into the host cell. We first generated single cell knockout clones deficient in some of the candidate genes for validation. We provide evidence that Polio Virus Receptor-related protein (PVRL2) serves as a receptor for BoHV-1, mediating more efficient entry than the previously identified Polio Virus Receptor (PVR). By knocking out two enzymes that catalyze HSPG chain elongation, HST2ST1 and GLCE, we further demonstrate the significance of HSPG in BoHV-1 entry. Another intriguing cluster of candidate genes, COG1, COG2 and COG4-7 encode six subunits of the Conserved Oligomeric Golgi (COG) complex. MDBK cells lacking COG6 produced fewer but bigger plaques compared to control cells, suggesting more efficient release of newly produced virions from these COG6 knockout cells, due to impaired HSPG biosynthesis. We further observed that viruses produced by the COG6 knockout cells consist of protein(s) with reduced N-glycosylation, potentially explaining their lower infectivity. To facilitate candidate validation, we also detailed a one-step multiplex CRISPR interference (CRISPRi) system, an orthogonal method to KO that enables quick and simultaneous deployment of three CRISPRs for efficient gene inactivation. Using CRISPR3i, we verified eight candidates that have been implicated in the synthesis of surface heparan sulfate proteoglycans (HSPGs). In summary, our experiments confirmed the two receptors PVR and PVRL2 for BoHV-1 entry into the host cell and other factors that affect this process, likely through the direct or indirect roles they play during HSPG synthesis and glycosylation of viral proteins.

Adeno-associated virus (AAV) has emerged as a leading platform for gene therapy, enabling the delivery of therapeutic DNA to target cells. However, the potential of AAV to deliver protein payloads has been unexplored. In this study, we engineered a protein carrier AAV (pcAAV) to package and deliver proteins by inserting binding domains on the interior capsid surface. These binding domains mediate the packaging of specific target proteins through interaction with cognate peptides or protein tags during the capsid assembly process. We demonstrate the packaging of multiple proteins, including green fluorescent protein, Streptococcus pyogenes Cas9, Cre recombinase, and the engineered peroxidase APEX2. Packaging efficiency is modulated by the binding domain insertion site, the viral protein isoform containing the binding domain, and the subcellular localization of the target protein. We show that pcAAV can enter cells and deliver the protein payload and that enzymes retain their activity after packaging. Importantly, this protein packaging capability can be translated to multiple AAV serotypes. Our work establishes AAV as a protein delivery vehicle, significantly expanding the utility of this viral vector for biomedical applications.