Biology subjects

Kan, A.

Publications and source records attributed to Kan, A..

6 recordsLinked to original sources

bioRxiv2024

Best Cochlear Locations for Delivering Interaural Timing Cues in Electric Hearing

Growing numbers of children and adults who are deaf are eligible to receive cochlear implants (CI), which provide access to everyday sound. CIs in both ears (bilateral CIs or BiCIs) are becoming standard of care in many countries. However, their effectiveness is limited because they do not adequately restore the acoustic cues essential for sound localization, particularly interaural time differences (ITDs) at low frequencies. The cochlea, the auditory sensory organ, typically transmits ITDs more effectively at the apical region, which is specifically "tuned" to low frequencies. We hypothesized that effective restoration of robust ITD perception through electrical stimulation with BiCIs depends on targeting cochlear locations that transmit information most effectively. Importantly, we show that these locations can occur anywhere along the cochlea, even on the opposite end of the frequency map from where ITD cues are most dominantly encoded in an acoustic hearing system.

neuroscience↗

bioRxiv2022

Metabolic interactions control the spread of plasmid-encoded functional novelty during microbial range expansion

Surface-associated microbial communities are omnipresent on Earth. As individuals grow and divide within these communities, they undergo range expansion during which different cell-types arrange themselves across space to form spatial patterns (referred to as spatial self-organization). Metabolic interactions are important determinants of the spatial self-organization process, where they direct the spatial positionings of different cell-types. We hypothesized here a previously unexplored consequence of metabolic interactions; by directing the spatial positionings of different cell-types, they also control the horizontal spread of functional novelty during range expansion. We focused on a form of functional novelty of critical importance to human health - the conjugative transfer and proliferation of plasmid-encoded antibiotic resistance. We performed range expansion experiments and spatially-explicit individual-based computational simulations with pairs of strains of the bacterium Pseudomonas stutzeri, where one strain was a plasmid donor and the other a potential recipient. We then imposed a competitive or resource cross-feeding interaction between them. We found that interactions that increase the spatial intermixing of strains also increase plasmid conjugation. We further directly linked these effects to spatial intermixing itself. We finally showed that the ability of plasmid recipients to proliferate is determined by their spatial positionings. Our results demonstrate that metabolic interactions are indeed important determinants of the horizontal spread of functional novelty during microbial range expansion, and that the spatial positionings of different cell-types need to be considered when predicting the proliferation and fate of plasmid-encoded traits.

ecology↗

bioRxiv2021

Programmable Microbial Ink for 3D Printing of Living Materials Produced from Genetically Engineered Protein Nanofibers

Living cells have the capability to synthesize molecular components and precisely assemble them from the nanoscale to build macroscopic living functional architectures under ambient conditions.1-3 The emerging field of living materials has leveraged microbial engineering to produce materials for various applications, but building 3D structures in arbitrary patterns and shapes has been a major challenge.1-14 We set out to develop a new bioink, termed as "microbial ink" that is produced entirely from genetically engineered microbial cells, programmed to perform a bottom-up, hierarchical self-assembly of protein monomers into nanofibers, and further into nanofiber networks that comprise extrudable hydrogels. We further demonstrate the 3D printing of functional living materials by embedding programmed Escherichia coli (E. coli) cells and nanofibers into microbial ink, which can sequester toxic moieties, release biologics and regulate its own cell growth through the chemical induction of rationally designed genetic circuits. This report showcases the advanced capabilities of nanobiotechnology and living materials technology to 3D-print functional living architectures.

synthetic biology↗

bioRxiv2020

Hybrid Living Capsules Autonomously Produced by Engineered Bacteria

Bacterial cellulose (BC) has excellent material properties and can be produced cheaply and sustainably through simple bacterial culture, but BC-producing bacteria lack the extensive genetic toolkits of model organisms such as Escherichia coli. Here, we describe a simple approach for producing highly programmable BC materials through incorporation of engineered E. coli. The acetic acid bacterium Gluconacetobacter hansenii was co-cultured with engineered E. coli in droplets of glucose-rich media to produce robust cellulose capsules, which were then colonized by the E. coli upon transfer to selective lysogeny broth media. We show that the encapsulated E. coli can produce engineered protein nanofibers within the cellulose matrix, yielding hybrid capsules capable of sequestering specific biomolecules from the environment and enzymatic catalysis. Furthermore, we produced capsules capable of altering their own bulk physical properties through enzyme-induced biomineralization. This novel system, based on autonomous biological fabrication, significantly expands the functionality of BC-based living materials.

synthetic biology↗

bioRxiv2019

Universal Loop assembly (uLoop): open, efficient, and species-agnostic DNA fabrication

Standardised Type IIS DNA assembly methods are becoming essential for biological engineering and research. Although a common syntax has been proposed to enable higher interoperability between DNA libraries, Golden Gate (GG)-based assembly systems remain specific to target organisms. Furthermore, these GG assembly systems become laborious and unnecessarily complicated beyond the assembly of 4 transcriptional units. Here, we describe \"universal Loop\" (uLoop) assembly, a simple system based on Loop assembly that enables hierarchical fabrication of large DNA constructs (> 30 kb) for any organism of choice. uLoop comprises two sets of four plasmids that are iteratively used as odd and even levels to compile DNA elements in an exponential manner (4n-1). The elements required for transformation/maintenance in target organisms are also assembled as standardised parts, enabling customisation of host-specific plasmids. Thus, this species-agnostic method decouples efficiency of assembly from the stability of vectors in the target organism. As a proof-of-concept, we show the engineering of multi-gene expression vectors in diatoms, yeast, plants and bacteria. These resources will become available through the OpenMTA for unrestricted sharing and open-access.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC=\"FIGDIR/small/744854v2_ufig.gif\" ALT=\"Figure 1\">\nView larger version (31K):\norg.highwire.dtl.DTLVardef@c36f4forg.highwire.dtl.DTLVardef@c0b007org.highwire.dtl.DTLVardef@64c810org.highwire.dtl.DTLVardef@8a94b0_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2017

Assessment of clonal kinetics reveals multiple trajectories of dendritic cell development

A thorough understanding of cellular development is incumbent on assessing the complexities of fate and kinetics of individual clones within a population. Here, we develop a system for robust periodical assessment of lineage outputs of thousands of transient clones and establishment of bona fide cellular trajectories. We appraise the development of dendritic cells (DCs) from barcode-labeled hematopoietic stem and progenitor cells (HSPCs) by serially measuring barcode signatures, and visualize this multidimensional data using novel developmental interpolated t-distributed stochastic neighborhood embedding (Di-SNE) time-lapse movies. We identify multiple cellular trajectories of DC development that are characterized by distinct fate bias and expansion kinetics, and determine that these are intrinsically programmed. We demonstrate that conventional DC and plasmacytoid DC trajectories are largely separated already at the HSPC stage. This framework allows systematic evaluation of clonal dynamics and can be applied to other steady-state or perturbed developmental systems.

systems biology↗