Biology subjects

Soffer, A.

Publications and source records attributed to Soffer, A..

3 recordsLinked to original sources

bioRxiv2024

Spectrin coordinates cortical actomyosin organization and differentiation essential for a functional epithelial barrier

Cell shape and fate are tightly linked, yet how the cortical cytoskeletal integrates regulation of shape and fate remains unclear. Using the epidermis as a paradigm where cell shape changes guide differentiation we identify spectrin as an essential organizer of the keratinocyte actomyosin cortex that integrates transitions in cell shape with spatial organization of signaling. Loss of II-spectrin (Sptan1) in the mouse epidermis altered cell shape in all layers and impaired differentiation, and barrier formation. High-resolution imaging and laser ablation revealed that E-cadherin guides differential gradients of actin and spectrin to regulate the layer-specific organization and mechanics of sub-membraneous spectrin-actomyosin networks. This organization is essential to dissipate tension, maintain structural integrity, and retain active growth factor receptor EGFR and the cation channel TRPV3 at the membrane in upper layers to induce terminal differentiation. Together, these findings reveal how organization of the cortical cytoskeleton coordinates changes in cell shape and cell fate at the tissue scale necessary to establish epithelial barriers.

cell biology↗

bioRxiv2020

Reconfiguring Okazaki fragment start sites on a genome by using a data driven approach

DNA-protein interactions are essential in all aspects of every living cell. Understanding of how features embedded in the DNA sequence affect specific interactions with proteins is challenging but important, since it may contribute to finding the means to regulate metabolic pathways involving DNA-protein interactions. Using a massive experimental benchmark dataset of binding scores for DNA sequences and a machine learning workflow, we describe the binding to DNA of T7 primase, as a model system for specific DNA-protein interactions. Effective binding of T7 primase to its specific DNA recognition sequences triggers the formation of RNA primers that serve as Okazaki fragment start sites during DNA replication.

biochemistry↗

bioRxiv2019

Novel lead compounds that target the ribosomal peptidyl transferase center

M. tuberculosis (Mtb) is a pathogenic bacterium that causes tuberculosis, which kills more than 1.5 million people worldwide every year. Strains resistant to available antibiotics pose a significant healthcare problem. The enormous complexity of the ribosome poses a barrier for drug discovery. We have overcome this in a tractable way by using an RNA segment that represents the peptidyl transferase center as a target. By using a novel combination of NMR transverse relaxation times (T2) and computational chemistry approaches, we have obtained improved inhibitors of the Mtb ribosomal PTC. Two phenylthiazole derivatives were predicted by machine learning models as effective inhibitors, and this was confirmed by their IC50 values, which were significantly improved over standard antibiotic drugs.

biochemistry↗