Prediction of strain engineerings that amplify recombinant protein secretion through the machine learning approach MaLPHAS.

This article presents a discussion of the process of precision fermentation (PF), describing the history of the space, the expected 70% growth over the next 5 years, various applications of precision fermented products, and the markets available to be disrupted by the technology. A range of prokaryotic and eukaryotic host organisms used for PF are described, with the advantages, disadvantages and applications of each. The process of setting up PF and strain engineering is described, as well as various ways that computational analysis and design techniques can be employed to assist PF engineering. The article then describes the design and implementation of a machine learning method, machine learning predictions having amplified secretion (MaLPHAS) to predict strain engineerings, which optimise the secretion of a recombinant protein. This approach showed an in silico cross-validated R 2 accuracy on the training data of up to 46.6% and in an in vitro test on a Komagataella phaffii strain, identified one gene engineering out of five predicted, which was shown to double the secretion of a heterologous protein and outperform three of the best-known edits from the literature for improving secretion in K. phaffii.

In vivo expansion of functionally integrated GABAergic interneurons by targeted increase in neural progenitors.

A central hypothesis for brain evolution is that it might occur via expansion of progenitor cells and subsequent lineage-dependent formation of neural circuits. Here, we report in vivo amplification and functional integration of lineage-specific circuitry in Drosophila Levels of the cell fate determinant Prospero were attenuated in specific brain lineages within a range that expanded not only progenitors but also neuronal progeny, without tumor formation. Resulting supernumerary neural stem cells underwent normal functional transitions, progressed through the temporal patterning cascade, and generated progeny with molecular signatures matching source lineages. Fully differentiated supernumerary gamma-amino butyric acid (GABA)-ergic interneurons formed functional connections in the central complex of the adult brain, as revealed by in vivo calcium imaging and open-field behavioral analysis. Our results show that quantitative control of a single transcription factor is sufficient to tune neuron numbers and clonal circuitry, and provide molecular insight into a likely mechanism of brain evolution.