Biology subjects

Lin, A.

Publications and source records attributed to Lin, A..

130 records · Page 8Linked to original sources

bioRxiv2018

Recombinant expression of Proteorhodopsin and biofilm regulators in Escherichia coli for nanoparticle binding and removal in a wastewater treatment model

The small size of nanoparticles is both an advantage and a problem. Their high surface-area-to-volume ratio enables novel medical, industrial, and commercial applications. However, their small size also allows them to evade conventional filtration during water treatment, posing health risks to humans, plants, and aquatic life. This project aims to remove nanoparticles during wastewater treatment using genetically modified Escherichia coli in two ways: 1) binding citrate-capped nanoparticles with the membrane protein Proteorhodopsin, and 2) trapping nanoparticles using Escherichia coli biofilm produced by overexpressing two regulators: OmpR234 and CsgD. We demonstrate experimentally that Escherichia coli expressing Proteorhodopsin binds to 60 nm citrate-capped silver nanoparticles. We also successfully upregulate biofilm production and show that Escherichia coli biofilms are able to trap 30 nm gold particles. Finally, both Proteorhodopsin and biofilm approaches are able to bind and remove nanoparticles in simulated wastewater treatment tanks. We envision integrating our trapping system in both rural and urban wastewater treatment plants to efficiently capture all nanoparticles before treated water is released into the environment.\n\nFinancial DisclosureThis work was funded by the Taipei American School. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\n\nCompeting InterestsThe authors have declared that no competing interests exist.\n\nEthics StatementN/A\n\nData AvailabilityYes - all data are fully available without restriction. Sequences for the plasmids used in this study are available through the Registry of Standard Biological Parts. Links to raw data are included in Supplementary Information.

synthetic biology↗

bioRxiv2017

Reciprocal Disruptions in Thalamic and Hippocampal Resting-State Functional Connectivity in Youth with 22q11.2 Deletions

22q11.2 deletion syndrome (22q11DS) is a recurrent copy number variant (CNV) with high penetrance for developmental neuropsychiatric disorders. Study of individuals with 22q11DS therefore may offer key insights into neural mechanisms underlying such complex illnesses. Resting-state functional MRI (rs-fMRI) studies in idiopathic schizophrenia have consistently revealed disruption of thalamic and hippocampal circuitry. Here, we sought to test whether this circuitry is similarly disrupted in the context of this genetic high-risk condition. To this end, resting-state functional connectivity patterns were assessed in a sample of young men and women with 22q11DS (n=42) and demographically matched healthy controls (n=39). Neuroimaging data were acquired via single-band protocols, and analyzed in line with methods provided by the Human Connectome Project (HCP). We computed functional relationships between individual-specific anatomically-defined thalamic and hippocampal seeds and all gray matter voxels in the brain. Whole-brain type I error protection was achieved through nonparametric permutation-based methods. 22q11DS patients displayed reciprocal disruptions in thalamic and hippocampal functional connectivity relative to control subjects. Thalamo-cortical coupling was increased in sensorimotor cortex, and reduced across associative networks. The opposite effect was observed for the hippocampus in regards to sensory and associative network connectivity. The thalamic and hippocampal dysconnectivity observed in 22q11DS suggest that high genetic risk for psychiatric illness is linked with disruptions in large-scale cortico-subcortical networks underlying higher-order cognitive functions. These effects highlight the translational importance of large-effect CNVs for informing mechanisms underlying neural disruptions observed in idiopathic developmental neuropsychiatric disorders.\n\nSIGNIFICANCE STATEMENTInvestigation of neuroimaging biomarkers in highly penetrant genetic syndromes represents a more biologically tractable approach to identify neural circuit disruptions underlying developmental neuropsychiatric conditions. 22q11.2 deletion syndrome confers particularly high risk for psychotic disorders, and is thus an important translational model in which to investigate systems-level mechanisms implicated in idiopathic illness. Here, we show resting-state fMRI evidence of large-scale sensory and executive network disruptions in youth with 22q11DS. In particular, this study provides the first evidence that these networks are disrupted in a reciprocal fashion with regard to the functional connectivity of the thalamus and hippocampus, suggesting circuit-level dysfunction.

neuroscience↗

bioRxiv2017

Combining CRISPR/Cas9 mutagenesis and a small-molecule inhibitor to probe the function of MELK in cancer

The Maternal Embryonic Leucine Zipper Kinase (MELK) has been identified as a promising therapeutic target in multiple cancer types. MELK over-expression is associated with aggressive disease, and MELK has been implicated in numerous cancer-related processes, including chemotherapy resistance, stem cell renewal, and tumor growth. On the basis of these findings, a MELK inhibitor is currently being tested in several clinical trials. Here, we report that cancer cell lines harboring CRISPR/Cas9-induced null mutations in MELK exhibit wild-type growth in vitro, under environmental stress, in the presence of multiple chemotherapy agents, and in vivo. By combining our MELK-knockout clones with a recently-described, highly-specific MELK inhibitor, we further demonstrate that the acute inhibition of MELK results in no specific anti-proliferative phenotype. Analysis of gene expression data from cohorts of cancer patients identifies MELK expression as a correlate of tumor mitotic activity, explaining its association with poor clinical prognosis. In total, our results demonstrate the power of CRISPR/Cas9-based genetic approaches to investigate cancer drug targets, and call into question the rationale for treating patients with anti-MELK monotherapies.

cancer biology↗

bioRxiv2017

Raspberry Pi Powered Imaging for Plant Phenotyping

O_LIPremise of the study: Image-based phenomics is a powerful approach to capture and quantify plant diversity. However, commercial platforms that make consistent image acquisition easy are often cost-prohibitive. To make high-throughput phenotyping methods more accessible, low-cost microcomputers and cameras can be used to acquire plant image data.\nC_LIO_LIMethods and Results: We used low-cost Raspberry Pi computers and cameras to manage and capture plant image data. Detailed here are three different applications of Raspberry Pi controlled imaging platforms for seed and shoot imaging. Images obtained from each platform were suitable for extracting quantifiable plant traits (shape, area, height, color) en masse using open-source image processing software such as PlantCV.\nC_LIO_LIConclusion: This protocol describes three low-cost platforms for image acquisition that are useful for quantifying plant diversity. When coupled with open-source image processing tools, these imaging platforms provide viable low-cost solutions for incorporating high-throughput phenomics into a wide range of research programs.\nC_LI

plant biology↗