Systems, methods and computer-readable media are provided for designing experiments for organisms at a first scale to generate first-scale performance data used in predicting performance of the organisms at a second, larger scale. The design includes determining first-scale screening conditions based at least in part upon the contribution of second-scale conditions to performance parameters of an organism at the second scale. The first-scale screening conditions include one or more proxies for second-scale conditions that cannot be replicated at first scale. The design determines first-scale screening parameters based at least in part upon computer modeling of the metabolism of the organism at the second scale.

Systems, methods and computer-readable media are provided for designing experiments for organisms at a first scale to generate first-scale performance data used in predicting performance of the organisms at a second, larger scale. The design includes determining first-scale screening conditions based at least in part upon the contribution of second-scale conditions to performance parameters of an organism at the second scale. The first-scale screening conditions include one or more proxies for second-scale conditions that cannot be replicated at first scale. The design determines first-scale screening parameters based at least in part upon computer modeling of the metabolism of the organism at the second scale.

Disclosed herein are methods and compositions useful for identification of potential therapeutic agents for the treatment of a NF1- or RAS-associated disorder. Disclosed herein are also methods and compositions useful for the treatment of a NF1- or RAS-associated disorder.

Disclosed is a high-throughput transcriptional assay format in Actinomycete bacteria, and Streptomyces spp. in particular, that leverages eGFP, inserted both at a neutral site and inside the biosynthetic cluster of interest, as a read-out for secondary metabolite synthesis. Using this approach, a silent gene cluster in Streptomyces albus J1074 was induced. The cytotoxins etoposide and ivermectin were revealed as potent inducers, allowing the isolation and structural characterization of nearly 20 novel small molecule products of the chosen cluster. One of these molecules is a novel antifungal, while several others inhibit a cysteine protease implicated in cancer. Studies addressing the mechanism of induction by the two elicitors led to the identification of a pathway-specific transcriptional repressor that silences the gene cluster under normal growth conditions. The successful implementation of this approach will allow future discovery of cryptic metabolites with useful bioactivities from Actinomycete bacteria.

In alternative embodiments, provided are compositions and methods for making a chimeric polypeptide comprising an S-layer polypeptide and a heterologous polypeptide or peptide. In alternative embodiments, the compositions and methods comprise recombinantly engineering a methylotrophic or methanotrophic bacteria to recombinantly express a chimeric polypeptide comprising an S-layer polypeptide and a heterologous polypeptide or peptide. Also provided are compositions and methods for displaying or immobilizing proteins on a methanotrophic S-layer. In alternative embodiments, provided are compositions and methods comprising recombinant methylotrophic or methanotrophic bacteria comprising assembled or self-assembled recombinant or isolated chimeric S-layer polypeptides. In alternative embodiments, provided are compositions and methods using recombinant methylotrophic or methanotrophic bacteria, optionally a Methylomicrobium alcaliphilum, optionally a M. alcaliphilum sp. 20Z, for ectoine ((4S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid), for the production or synthesis of a protein, e.g., an ectoine, or an enzyme, e.g., a lipase.

Provided herein are novel organoid culture media, organoid culture systems, and methods of culturing tumor organoids using the subject organoid culture media. Also provided herein are tumor organoids developed using such organoid culture systems, methods for assessing the clonal diversity of the tumor organoids, and methods for using such tumor organoids, for example, for tumor modelling and drug development applications. In particular embodiments, the tumor organoid culture media provided herein is substantially free of R-spondins (e.g., R-spondin1).

The disclosure relates to a biosensor on the bacterial cell surface for sensing and responding to extracellular molecules. Related methods of using the bacterial cells to inducibly express a protein of interest and/or a bioactive RNA molecule in a subject are disclosed. Related methods of using the bacterial cells to inducibly express a protein of interest or to detect a target of interest in a sample are also disclosed.

The present invention provides markers for judging the efficacy of therapy with a PD-1 signal inhibitor before or at an early stage of the therapy. As biomarkers for predicting or judging the efficacy of therapy with a PD-1 signal inhibitor, surrogate indicators of metabolic changes relating to mitochondrial activity in T cells and/or T cell activation in a subject are used. As such indicators, intestinal flora-related metabolites in the serum or plasma, energy metabolism-related metabolites in the serum or plasma, amino acid metabolism-related metabolites and/or derivatives thereof in the serum of plasma, oxygen consumption rate and/or ATP turnover in peripheral blood CD8.sup.+ cells, amino acids in T cells, and T-bet in peripheral blood CD8.sup.+ cells may be used.

Provided are assay systems for determining the therapeutic or toxic effect of a putative drug based on assaying its activity in cells which have been differentiated in vitro from stem cells, and induced to display a phenotype that resembles a disease to be treated.

The present invention relates to methods and compositions for inhibiting metastatic spread of cancer and/or inhibiting progression of pre-existing metastatic disease in a subject using L1CAM inhibition.