It has been a couple of very intense and pleasantly sunny days at the Biophysical Society thematic meeting in Ascona. As Marina mentioned in the previous post we have had the chance to learn lots of new things so far. My poster presentation involved shaking elbows with one of the official judges of the poster session, Steven Boxer, answering his questions and showing movies of coarse grained MD simulations. Following the line of Marina’s post the next short paragraphs summarise the highlights of the second day.
Before starting with the summary, on the first day of the meeting Reinhard Jahn gave a very interesting evening lecture on molecular steps in SNARE-mediated membrane fusion. The main highlights of his talk were: the membrane fusion zippering hypothesis of SNARE function, the fusion of injected artificial vesicles containing SNARE proteins with their endogenous counterparts and the SNARE mimicry by proteins from Legionella bacteria.
Wolfhard Almers showed how exocytosis and secretion in a chromaffin cell depend on calcium concentration and how the clusters of syntaxin-1A, a member of the SNARE proteins family, in granules are involved in the docking to the plasma membrane.
Lawry Rajendran described the role of endosomes and exosomes in the generation and release of amyloids in Alzheimer’s disease, in which insulin nutrient amino acids suppress lysosomes formation and promote amyloid-beta peptides release. The inhibition of insulin/IGF1/nutrient (IIN) was shown to promote lysosomes biogenesis and reduce the amyloid-beta peptide formation. Interestingly, the overnutrition can induce the production of more amyloid peptides, while different diets can reduce it. He also introduced an interesting initiative named Science Matters, which is devoted to the promotion of single observation publishing with a triple blinded peer review process.
Muhmmad Omar Hmeadi talked about the PIP2 regulation of exocytosis and its colocalization in the plasma membranes, which were investigated by confocal and TIRF microscopy to study microdomains of PIP2. He also showed that syntaxin clusters are formed at docked granule sites, the chemically induced depletion of PIP2 in the PM did not affect docking but inhibited exocytosis and more colocalization of PIP2 in the presence of alpha toxin.
Christopher Stroupe showed how membranes must tether before they can fuse and the molecular nature of tethering interaction for the yeast vacuolar protein, Ypt7p, and HOPS protein, which is required for Ebola virus entry.
David Alsteens presented how imaging individual receptors can be used to extract kinetic and thermodynamic parameters using FD-based AFM, which is a technique that allows to detect chemical groups on single native proteins with a 5 nm resolution and to probe the free energy landscape of a receptor-ligand complex.
Jay Groves talked about biochemical signalling reactions on membrane surfaces, in particular tyrosine phosphorylations, which can induce totally reversible protein receptors phase transitions. The kinetic phases of two PIP lipids, PIP1 and PIP2, were
bistable with the reaction size directing the chemical outcome.
Botond Roska described the process of differentiation of iPSCs into human starburst cells and brain, which can be used to form a retina in vitro and gene therapy approaches that could treat genetic eye diseases.
Nikhil Gandasi showed that the assembly of the secretory machinery during insulin granule docking leads to the formation of the formation of hundreds of granules that can fuse and release insulin decreasing the blood glucose. Syntaxin is recruited during the docking and it stays on the membrane acting like a glue.
Joel de Beer talked about fusing extracellular vesicles (which represent an evolutionary conserved communication systems, have sizes from 30 to 150 nm, a special lipid composition and a unique secretion mechanism) with synthetic liposomes,. He also showed how to transform from EVs to drug carriers using the fusion between synthetic and native vesicles, leading to the formation of liposomes named hybridosomes.
Raya Sorkin showed the soft side of extracellular vesicles (EVs) formed from red blood cells by measuring the bending modulus of pressurized vesicles. Her studies confirmed that pure lipid vesicles are stiffer than EVs and that the presence of antimicrobial peptides, alamethicin and magainin, in DOPC and POPC lipid bilayers reduces the bending modulus of these systems making them softer.
After another very lively and warm poster session, Anthony Hyman gave a very interesting talk on how different non membrane bound cell compartments, such as P granules and nucleoli, undergo phase transitions and behave like viscous liquids. He also showed that prion-like proteins concentrated in stress granules can be reconstituted in vitro and are subjected to an aging process leading to the formation of fibers and aggregates in few hours time. Since many of prion-like proteins behave similarly, these aberrant phase transitions may drive neurodegeneration. The formation of liquid droplets promotes biochemistry via RNA, while the presence of solid aggregates shuts down the biochemistry of a living cell.
Gunnar von Heijne gave a really interesting evening lecture on how arrest peptides can be used as force sensors to study cotranslational processes by measuring pulling forces generated by the folding of protein sequences stuck in the ribosome. The cotranslational folding of cytoplasmic proteins involves the folding of the protein inside the ribosome generating a strong pulling force. Different mutations of the protein spectrin are subjected to pulling forces ranging from 10 to 20 pN and are associated with different folding pathways in vitro and in ribosomo.
The day ended with a late night poster session for three attendees, lots of drinking and socialising…