Alternative sigma factor over-expression enables heterologous expression of a type II polyketide biosynthetic pathway in Escherichia coli.

Background: Heterologous expression of bacterial biosynthetic gene clusters is currently an indispensable tool for characterizing biosynthetic pathways. Development of an effective, general heterologous expression system that can be applied to bioprospecting from metagenomic DNA will enable the discovery of a wealth of new natural products.

Methodology: We have developed a new Escherichia coli-based heterologous expression system for polyketide biosynthetic gene clusters.

Virus-tumor interactome screen reveals ER stress response can reprogram resistant cancers for oncolytic virus-triggered caspase-2 cell death.

To identify therapeutic opportunities for oncolytic viral therapy, we conducted genome-wide RNAi screens to search for host factors that modulate rhabdoviral oncolysis. Our screens uncovered the endoplasmic reticulum (ER) stress response pathways as important modulators of rhabdovirus-mediated cytotoxicity. Further investigation revealed an unconventional mechanism whereby ER stress response inhibition preconditioned cancer cells, which sensitized them to caspase-2-dependent apoptosis induced by a subsequent rhabdovirus infection.

Non-multipotent stroma inhibit the proliferation and differentiation of mesenchymal stromal cells in vitro.

Background Aims: The ability to expand and maintain bone marrow (BM)-derived mesenchymal stem cells (MSC) in vitro is an important aspect of their therapeutic potential. Despite this, the exact composition of stromal cell types within these cultures and the potential effects of non-stem cells on the maintenance of MSC are poorly understood.

Methods: C57BL/6J BM stroma was investigated as a model to determine the relationship between MSC and non-multipotent cells in vitro.