J. Frydman

SARS-CoV-2 Nsp1 regulates translation start site fidelity to promote infection

This study identifies Nsp1's role in enhancing SARS-CoV-2 translation by interacting with EIF1A, leading to reduced viral titers when EIF1A is depleted.

Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease

This study uses transdifferentiated neurons to show lysosomal deficits are an early event in aging and Alzheimer's disease, leading to proteotoxic deposits and cell death.

A structural vista of phosducin-like PhLP2A-chaperonin TRiC cooperation during the ATP-driven folding cycle

This paper reveals the ATP-driven structural rearrangement of PhLP2A during TRiC-mediated protein folding using cryoEM and biochemical analyses.

An ESCRT-dependent pathway of Nuclear and Cytoplasmic Spatial PQC is coordinated at Nuclear Vacuolar Junctions

The paper identifies an ESCRT-dependent pathway that coordinates nuclear and cytoplasmic protein quality control (PQC) at nuclear-vacuolar junctions, enabling vacuolar clearance of misfolded proteins.

An mTOR-independent Macroautophagy Activator Ameliorates Tauopathy and Prionopathy Neurodegeneration Phenotypes

The paper identifies CCT020312, an mTOR-independent autophagy activator, which reduces tauopathy and prionopathy neurodegeneration phenotypes by enhancing autophagy flux and clearing protein aggregates.

Cancers adapt to their mutational load by buffering protein misfolding stress

The paper shows high mutational load tumors upregulate proteostasis machinery to buffer protein misfolding stress, revealing therapeutic vulnerabilities.

Structural visualization of the tubulin folding pathway directed by eukaryotic chaperonin TRiC

The paper visualizes the tubulin folding pathway mediated by TRiC using cryoEM, showing how TRiC's structure guides the folding of β-tubulin through specific interactions.

A Lethal Genetic Incompatibility between Naturally Hybridizing Species in Mitochondrial Complex I

The paper identifies a lethal mitonuclear incompatibility in swordtail fish hybrids involving three Complex I genes, showing non-additive genetic effects and inter-species transfer of incompatibility.

The unfolded protein response of the endoplasmic reticulum supports mitochondrial biogenesis by buffering non-imported proteins

The paper shows that mitochondrial membrane proteins accumulate in the endoplasmic reticulum during import defects, triggering the UPRER to maintain protein homeostasis.

Multi-Scale 3D Cryo-Correlative Microscopy for Vitrified Cells

This paper introduces a multi-scale 3D cryo-correlative microscopy pipeline for visualizing vitrified cells, demonstrating its application to heat-shocked yeast cells.

Principles of dengue virus evolvability derived from genotype-fitness maps in human and mosquito cells

This study identifies principles of dengue virus evolvability by analyzing genotype-fitness maps in human and mosquito cells, revealing host-specific adaptation mechanisms and genetic load effects.

REP-X: An Evolution-guided Strategy for the Rational Design of Cysteine-less Protein Variants

The paper introduces REP-X, a tool that uses evolutionary information to design cysteine-less protein variants while maintaining activity and stability.

Hsp90 dictates viral sequence space by balancing the evolutionary tradeoffs between protein stability, aggregation and translation rate

The paper shows that reducing Hsp90 activity increases viral sequence diversity by altering the balance between protein stability, aggregation, and translation rate.