How can a cytosolic autophagy machinery "eat" parts of the nucleus? New work from LusKing and Melia labs provide an answer.
It is known that pathological protein aggregates can accumulate within the nucleus and can be cleared by a cytosolic autophagy machinery. However, the underlying mechanisms that allow the autophagosome to "see" aberrant proteins that are hidden by the double membrane of the nuclear envelope remains unknown. In a collaborative work, Sunandini Chandra, Philip Mannino and David Thaller provide compelling new evidence for an outside-in mechanism where a transmembrane cargo adaptor localizes at the outer nuclear membrane and reaches across the nuclear envelope lumen to capture the inner nuclear membrane into vesicles that can be ultimately captured by the autophagosome.Source: Journal of Cell Biology
A DNA-origami NanoTrap for studying the diffusion barriers
DNA nanotechnology provides a versatile and powerful tool to dissect the structure-function relationship of biomolecular machines like the nuclear pore complex (NPC), an enormous protein assembly that controls molecular traffic between the nucleus and cytoplasm. To understand how the intrinsically disordered, Phe-Gly-rich nucleoporins (FG-nups) within the NPC’s central transport channel impede the diffusion of macromolecules, Yale researchers built a DNA-origami NanoTrap. The NanoTrap comprises precisely arranged FG-nups in an NPC-like channel, which sits on a baseplate that captures macromolecules that pass through the FG network. The DNA-origami based nuclear pore mimics can now trap molecules and test how FG-nups form diffusion barriers within nanopore confinement. Published in the BioRxiv, Qi Shen leading the collaboration with Chenxiang Lin (Cell Biology & Nanobiology Institute) and Patrick Lusk (Cell Biology).Source: BioRxiv
The LusKing lab discovers role for phosphatidic acid in nuclear envelope surveillance
Small holes in the nuclear membranes lead to the recruitment of the endosomal sorting complexes required for transport (ESCRT), which seal the holes and protect the integrity of the nucleus. New work from the LusKing group has discovered that a key element of this surveillance pathway is the directly binding of a key nuclear envelope ESCRT, Chm7 to phosphatidic acid rich membranes.Source: BioRxiv
Two From Yale Are Named Allen Distinguished Investigators
Megan C. King, PhD, associate professor of cell biology and of molecular, cellular and developmental biology, and Simon Mochrie, PhD, professor of physics and of applied physics, have been named Allen Distinguished Investigators by The Paul G. Allen Frontiers Group, a division of the Allen Institute.
In the right (lab) culture, mentorship flourishes — and science benefits
You might imagine a science lab looking a bit sterile and impersonal — little sunlight, masked figures in white coats pouring neon-colored liquid into beakers, all business. You might not expect to hear a science lab referred to as familial, where badminton tournaments, movie nights and barbeques are commonplace.
David Thaller wins the Porter Prize for Research Excellence
ASCB’s Award Selection Committee has chosen Meng-meng Fu, a postdoctoral fellow at Stanford University, and David Thaller, a PhD candidate from the Lusk lab at Yale University, as the 2019 winners of the Porter Prizes for Research Excellence.Source: The American Society for Cell Biology
Newly Funded Chromatin Study Could Shed Light on Genome
Combining engineering, biology and physics, three Yale researchers have received a four-year grant from the National Science Foundation (NSF) to study chromatin in yeast cells. They aim to better understand chromatin's properties and use the genome as a device to measure and record dynamic, transient chromatin states.
Action of ‘molecular bouncers’ captured at model of nuclear membrane
DNA is packaged tightly within the cell’s nuclear membranes, which contain channels that regulate the transit of macromolecules governing all of life’s functions. Yale University researchers have built a nanoscale replica of this channel and have visualized the interaction of proteins that act as “molecular bouncers,” controlling access to the channel’s 40-nanometer entrance.