Podcasts about endosome

The potential of mRNA medicines was postulated for years, but it took the COVID pandemic and emergency use authorizations for that potential to be demonstrated. By now, most of us have received at least one mRNA based vaccine and the platform has been mostly derisked. However, if you're not one of the major players in this space, generating high-purity mRNA, let alone a GMP-grade mRNA-based drug product, can still be quite challenging. Dr. Chrisitan Cobaugh, CEO of Vernal Biosciences in Vermont, has been working in the mRNA field for more than a decade and is passionate about the potential of mRNA medicines. He's also been in the field long enough to know firsthand the challenges of high-purity mRNA and lipid nanoparticle supply. Join us as Christian walks us through his story, the start of Vernal Biosciences, and their progress toward their mission of democratizing access to mRNA technology. Our conversation touches on the molecular biology of making mRNA, and the use of digital PCR and other methods in monitoring development and release of mRNA drug products, and the potential applications of mRNA as a platform (some of which you might not have guessed).Whether you're new to the technology, or have chosen mRNA as a focus area, you're sure to find this conversation engaging and intriguing, and our guest insightful. Visit the Absolute Gene-ius page to learn more about the guests, the hosts, and the Applied Biosystems QuantStudio Absolute Q Digital PCR System. 

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.15.549172v1?rss=1 Authors: Zheng, J.-X., Du, T.-Y., Shao, G.-C., Ma, Z.-H., Jiang, Z.-D., Hu, W., Suo, F., He, W., Dong, M.-Q., Du, L.-L. Abstract: Killer meiotic drivers (KMDs) skew allele transmission in their favor by killing meiotic progeny not inheriting the driver allele. Despite their widespread presence in eukaryotes, the molecular mechanisms behind their selfish behavior are poorly understood. Here we investigate how the poison and antidote products of a fission yeast wtf-family KMD gene can act antagonistically. Both the poison and the antidote are multi-transmembrane proteins, differing only in their N-terminal cytosolic tails. We find that the antidote employs N-terminal PY motifs to bind Rsp5/NEDD4 family ubiquitin ligases, which ubiquitinate the antidote. Mutating PY motifs or attaching a deubiquitinating enzyme transforms the antidote into a toxic protein. Ubiquitination promotes the transport of the antidote from the trans-Golgi network to the endosome, thereby neutralizing its toxicity and that of the bound poison. We propose that post-translational modification-mediated protein localization and/or activity changes may be a common mechanism governing the antagonistic duality of single-gene KMDs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.06.547997v1?rss=1 Authors: Suzuki, S., West, M., Zhang, Y., Fan, J. S., Roberts, R. T., Odorizzi, G., Emr, S. D. Abstract: Endosomes are specialized organelles that function in the secretory and endocytic protein sorting pathways. Endocytosed cell surface receptors and transporters destined for lysosomal degradation are sorted into intralumenal vesicles (ILVs) at endosomes by Endosomal Sorting Complex Required for Transport (ESCRT) proteins. The endosomes (multivesicular bodies, MVBs) then fuse with the lysosome. During endosomal maturation, the number of ILVs increases, but the size of endosomes does not decrease despite consumption of the limiting membrane during ILV formation. Vesicle-mediated trafficking is thought to provide lipids to support MVB biogenesis. However, we have uncovered an unexpected contribution of a large bridge-like lipid transfer protein, Vps13, in this process. Here, we reveal that Vps13-mediated lipid transfer at ER-endosome contact sites is required for the ESCRT pathway. We propose that Vps13 may play a critical role in supplying lipids to the endosome, ensuring continuous ESCRT-mediated sorting during MVB formation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.05.535676v1?rss=1 Authors: Brault, J.-B., Liu, Z., Bardin, S., Ladarre, D., Fraisier, V., Tchenio, A., Lenkei, Z., Salamero, J., Delevoye, C., Goud, B., Miserey, S. Abstract: Alzheimer s disease (AD) is the most common form of dementia worldwide. One of AD s main pathological hallmarks is the cerebral plaque deposits of Beta-amyloid (ABeta). ABeta is generated through sequential enzymatic cleavage of the amyloid precursor protein (APP). The Beta-secretase or Beta-site APP-cleaving enzyme 1 (BACE1) initiates this cleavage and is thus key to regulate ABeta formation. Both APP and BACE1 transit through the endolysosomal system but the exact nature of the compartment(s) where APP cleavage occurs as well as the molecular mechanisms that govern their endosomal sorting remain poorly known. Here we show that RAB11 not only regulates BACE1 transport from early/sorting endosomes (EEs/SEs) and drives the exocytosis of BACE1-containing recycling carriers. Moreover, recycling endosome-associated KIF13A, as well as its closely related homolog KIF13B, which are known RAB11 effectors involved in the biogenesis of recycling endosome (RE) from EEs/SEs, also participate in BACE1 endosomal sorting. Importantly, depletion of KIF13A or KIF13B leads to an increase in ABeta generation. Depletion of the BLOC-1 complex, previously described as an essential partner for KIF13A-dependent RE biogenesis, also induces increased amount of ABeta. Altogether, our findings support a model where the EEs/SEs represent a major organelle for ABeta formation and identify the recycling endosome biogenesis machinery as a master coordinator of BACE1 endosomal sorting and transport. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.27.534325v1?rss=1 Authors: Nagano, M., Aoshima, K., Shimamura, H., Siekhaus, D. E., Toshima, J. Y., Toshima, J. Abstract: Clathrin-mediated vesicle trafficking plays central roles in the post-Golgi transport pathways from the trans-Golgi network (TGN) to endosomes. In yeast, two clathrin adaptors - AP-1 complex and GGA proteins (GGAs) - are predicted to generate distinct transport vesicles at the TGN, and epsin-related Ent3p/Ent5p act as accessories for these adaptors. Recently, we showed that vesicle transport from the TGN, rather than from the plasma membrane, is crucial for Rab5-mediated endosome formation, and that Ent3p/5p are crucial for this process, whereas AP-1 and GGAs are dispensable. However, these observations were incompatible with previous studies showing that these adaptors are required for Ent3p/5p recruitment to the TGN, and thus the overall mechanism responsible for regulation of Rab5 activity remains ambiguous. Here we investigated the functional relationships between clathrin adaptors in post-Golgi-mediated Rab5 activation. We were able to show that AP-1 disruption in ENT3/ENT5-deleted mutant impairs Rab5-GEF Vps9p transport to the Rab5 compartment, and severely reduces Rab5 activity. Additionally, GGAs, Golgi-resident PI4 kinase Pik1p and Rab11 GTPases Ypt31p/32p were found to have partially overlapping functions for recruitment of AP-1 and Ent3p/5p to the TGN. These findings suggest a distinct role of clathrin adaptors for Rab5 activation in the TGN-endosome trafficking pathway. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.01.530579v1?rss=1 Authors: Borchers, A.-C., Janz, M., Schaefer, J.-H., Moeller, A., Kuemmel, D., Paululat, A., Ungermann, C., Langemeyer, L. Abstract: Maturation from early to late endosomes depends on the exchange of their marker proteins Rab5 to Rab7. This requires Rab7 activation by its specific guanine nucleotide exchange factor (GEF) Mon1-Ccz1. Efficient GEF activity of this complex on membranes depends on Rab5, thus driving Rab-exchange on endosomes. However, molecular details on the role of Rab5 in Mon1-Ccz1 activation are unclear. Here we identify key features in Mon1 involved in GEF regulation. We show that the intrinsically disordered N-terminal domain of Mon1 autoinhibits Rab5-dependent GEF-activity on membranes. Consequently, Mon1 truncations result in higher GEF activity in vitro, and a shift from Rab5 to more Rab7 positive structures in Drosophila nephrocytes and yeast, suggesting faster endosomal maturation. Using modeling, we further identify a conserved Rab5 binding site in Mon1. Mutations impairing Rab5 interaction result in poor GEF activity on membranes and growth defects in vivo. Our analysis provides a framework to understand the mechanism of Rab-conversion and organelle maturation along the endomembrane system. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

The TWiPsids solve the case of the Guatemalan Positive for Rhinovirus, and reveal how to kill all African trypanosomes with a primate apolipoprotein. Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin Become a patron of TWiP. Links for this episode: APOLs kill all African trypanosomes (Nat Micro) Trypanocidal properties of APOL1 on TWiP 85: Channeling tryps Letters read on TWiP 142 Case Study for TWiP 142 Woman in 50s, immigrant from rural area with limited resources. Admitted to hospital with iron deficient anemia and eosinophilia. In US. Sent for colonoscopy. Note long slender serpiginous motile object, recovered, 4.5 cm long, one end slender, other large and curled but not blunt. Send worm to parasitology lab for identification. What might fit description? Is this usually associated with eosinophilia? What about anemia, is severe or mild? Would this person have come from outside the US to acquire this, or could they have acquired the infection in the US. Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

Daniel and Vincent solve the case of the Woman With Anal Area Discomfort, and discuss the multiple functions of a clathrin adapter protein in formation of rhoptry and microneme secretory organelles of Toxoplasma gondii. Hosts: Vincent Racaniello and Daniel Griffin Become a patron of TWiP. Links for this episode: Journal of Microbiology and Biology Education SciComm Issue (link) TWiP 19: Enterobius vermicularis, the pinworm Multiple roles of Toxoplasma gondii clathrin adaptor AP1 protein (PLoS Path) Image credit Letters read on TWiP 133 Case Study for TWiP 133 Seen while working in remote mountain makeshift mobile clinic in Dominican Republic, on Haitian border. Traveled 3 h by pickup truck, remote mountain town, womens centers. Set up makeshift mobile clinic in this center. Mother concerned about 6 yo girl, failure to thrive compared with sister, protuberant belly, frequent abdominal discomfort, going on over 1 year. No surgeries, no meds, first time ever seeing medical person. Mother and sister are family. Three children in family. Father does timber work. Very impoverished region, living in dirt floor home, drinking untreated water from local stream, go to bathroom outside, could be contamination. Diet: carbohydrate, plantains, rice, beans. On exam: lungs clear, heart fine, belly protuberant, liver and spleen not enlarged, some edema. Mother said noticed long motile worm in girls feces. Firm belly, not painful to her. Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

An iron hand controls endosome-mitochondria contacts In erythroid cells, endocytosed iron is directly transferred into mitochondria at dynamic endosome-mitochondria contacts. Das et al. reveal that this process also occurs in epithelial cells, and that the motility of endosomes, and the duration of their interactions with mitochondria, is modulated by intra-endosomal iron release from transferrin. This biosights episode presents the paper by Das et al. from the September 26th, 2016, issue of The Journal of Cell Biology and includes an interview with the paper's senior author, Margarida Barroso (Albany Medical College, Albany, NY). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research. Subscribe to biosights via iTunes or RSS View biosights archive The Rockefeller University Press biosights@rockefeller.edu

Host: Vincent Racaniello Guests: Ruth Jarrett, Glen Nemerow, and Esther Schnettler At the Glasgow Science Festival microTALKS, Vincent speaks with Ruth, Glen, and Esther about their research on viruses and Hodgkin lymphoma, adenovirus structure and entry into cells, and interactions between arthropod borne viruses and their hosts. Links for this episode Glasgow Science Festival microTALKS Hodgkin lymphoma (Histopath) HHV-6 and Hodgkin lymphoma (PLoS One) Adenovirus entry (PLoS Path) Adenovirus membrane penetration (Virology) Mosquito pathways that limit CHIK replication (PLoS Negl Trop Dis) Tick antiviral RNAi (Nucl Acids Res) Video of this episode - view at YouTube Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv

Host: Vincent Racaniello Guests: Kartik Chandran, Ganjam Kalpana, and Margaret Kielian Vincent travels to Albert Einstein College of Medicine where he speaks with Kartik, Ganjam, and Margaret about their work on Ebolavirus entry, a tumor suppressor that binds the HIV-1 integrase, and the entry of togaviruses and flaviviruses into cells. Links for this episode Antibodies that protect against Sudan virus (ACS Chem Biol) Ebola virus entry requires NPC1 (EMBO J) A toggle switch for virus entry (Nat Comm) Imaging alphavirus exit (J Virol) Defects in HIV-1 unable to interact with INI1 (Retrovirol) Cell cycle arrest by INI1 (Mol Cell Biol) Video of this episode - view at YouTube Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv

Nick Gay discusses how the adaptor protein TMED7 targets the pathogen-sensing receptor TLR4 to the plasma membrane.

Carlos Gorbea discusses how a subset of proteasomes attenuates TLR3-mediated antiviral signaling.

Sat, 1 Jan 1994 12:00:00 +0100 http://epub.ub.uni-muenchen.de/4054/ http://epub.ub.uni-muenchen.de/4054/1/035.pdf Plank, Christian; Oberhauser, Berndt; Mechtler, Karl; Koch, Christian; Wagner, Ernst Plank, Christian; Oberhauser, Berndt; Mechtler, Karl; Koch, Christian und Wagner, Ernst (1994): The influence of endosome-disruptive peptides on gene transfer using synthetic virus-like gene transfer systems. In: Journal of Biological Chemistry, Vol. 269: pp. 12918-12924.

Wed, 1 Jan 1992 12:00:00 +0100 http://epub.ub.uni-muenchen.de/4042/ http://epub.ub.uni-muenchen.de/4042/1/021.pdf Cotten, Matt; Wagner, Ernst; Zatloukal, Kurt; Phillips, Stephen; Curiel, David T.; Birnstiel, Max L. Cotten, Matt; Wagner, Ernst; Zatloukal, Kurt; Phillips, Stephen; Curiel, David T. und Birnstiel, Max L. (1992): High-efficiency receptor-mediated delivery of small and large (48 kilobase gene constructs using the endosome-disruption activity of defective or chemically inactivated adenovirus particles. In: Proceedings of the National Academ