Biology subjects

Kibler, R.

Publications and source records attributed to Kibler, R..

3 recordsLinked to original sources

bioRxiv2023

A Generative Model for Creating Path Delineated Helical Proteins

Engineered proteins with precisely defined shapes can scaffold functional protein domains in 3D space to fine-tune their functions, such as the regulation of cellular signaling by ligand positioning or the design of self-assembling protein materials with specific forms. Methods for simply and efficiently generating the protein backbones to initiate these design processes remain limited. In this work, we develop a lightweight neural network to guide helix fragment assembly along a guideline using a GAN architecture and show that this approach can rapidly generate viable samples while being computationally inexpensive. Key to our approach is the transformation of the input structural data used for training into a parametric representation of helices to reduce the generator network size, which in turn facilitates rapid backpropagation to find specific helical arrangements during generation. This approach provides a method to quickly generate helical protein scaffolds.

synthetic biology↗

bioRxiv2022

Precisely patterned nanofibers made from extendable protein multiplexes

Molecular systems with coincident cyclic and superhelical symmetry axes have considerable advantages for materials design as they can be readily lengthened or shortened by changing the length of the constituent monomers. Among proteins, alpha helical coiled coils have such symmetric extendable architectures, but are limited by the relatively fixed geometry and flexibility of the helical protomers. Here, we describe a systematic approach to generating modular and rigid repeat protein oligomers with coincident C2 to C8 and superhelical symmetry axes that can be readily extended by repeat propagation. From these building blocks, we demonstrate that a wide range of unbounded fibers can be systematically designed by introducing hydrophilic surface patches that force staggering of the monomers; the geometry of such fibers can be precisely tuned by varying the number of repeat units in the monomer and the placement of the hydrophilic patches.

bioengineering↗

bioRxiv2019

Microbial single-cell RNA sequencing by split-pool barcoding

Single-cell RNA-sequencing (scRNA-seq) has become an essential tool for characterizing multi-celled eukaryotic systems but current methods are not compatible with bacteria. Here, we introduce microSPLiT, a low cost and high-throughput scRNA-seq method that works for gram-negative and gram-positive bacteria and can resolve transcriptional states that remain hidden at a population level. We applied microSPLiT to >25,000 Bacillus subtilis cells sampled from different growth stages, creating a detailed atlas of changes in metabolism and lifestyle. We not only retrieve detailed gene expression profiles associated with known but rare states such as competence and PBSX prophage induction, but also identify novel and unexpected gene expression states including heterogeneous activation of a niche metabolic pathway in a subpopulation of cells. microSPLiT empowers high-throughput analysis of gene expression in complex bacterial communities.

bioengineering↗