Biology subjects

Wu, S.-J.

Publications and source records attributed to Wu, S.-J..

5 recordsLinked to original sources

bioRxiv2023

Transcriptome and Mutant Analysis of Neuronal Genes for Memory Formation and Retrieval in Caenorhabditis elegans

Although it is generally believed that the formation and retrieval of memory require distinct sets of genes, little is known about the identity and temporal specificity of genes that act at different memory stages. Here we characterize the transcriptomes for the formation and retrieval of stress-induced aversive memory in the nematode Caenorhabditis elegans. Our RNA-sequencing analysis show that neuronal genes for calcium homeostasis, membrane excitability, synaptic function and signaling are progressively activated during the formation of aversive memory. Stage-specific transcriptomes further reveal that memory formation and retrieval display distinct gene activation patterns. We carried out a candidate screen of mutants for these memory genes and verified the temporal requirement of memory function for several of them. Further in-depth characterization of casy-1/calsyntenin show that while the short CASY-1B isoform acts in memory retrieval, the long CASY-1A isoform functions during memory formation, and its shed extracellular N-terminus fragment is likely a critical signal for memory regulation. Our work uncovers gene expression patterns associated with distinct memory stages and provides a foundation for future mechanistic interrogation of memory functions.

neuroscience↗

bioRxiv2023

Directed evolution of nanosensors for the detection of mycotoxins

In this study, we develop and apply a directed evolution approach to engineer the optical sensing properties of DNA-wrapped single-walled carbon nanotubes (DNA-SWCNTs) towards mycotoxins, a class of molecules critical to detect in the food industry. We successfully demonstrate the creation of sensors for the detection of both the aflatoxin B1 (AFB1) and fumonisin B1 (FB1) mycotoxins based on the specific response of the (9,4) and (7,5) SWCNT chirality fluorescence peaks, respectively. The resulting chirality-specific responsivity was used to demonstrate the multimodal detection of both mycotoxins at different wavelengths of light in the presence of complex food medium. Moreover, we show that directed evolution can be used not only to improve the chiral-dependent selectivity of our sensors to the mycotoxins, but also the sensor sensitivity and fluorescence intensity through multiple rounds of evolution. The approach demonstrated in this study is versatile and could be generalized to other SWCNT sensors as well as other nanosensors comprising a biological element.

biophysics↗

bioRxiv2021

Homo-harringtonine (HHT) - A highly effective drug against coronaviruses and the potential for large-scale clinical applications

In the search for treatment schemes of COVID-19, we start by examining the general weakness of coronaviruses and then identify approved drugs attacking that weakness. The approach, if successful, should identify drugs with a specific mechanism that is at least as effective as the best drugs proposed and are ready for clinical trials. All coronaviruses translate their non-structural proteins ([~]16) in concatenation, resulting in a very large super-protein. Homo-harringtonine (HHT), which has been approved for the treatment of leukemia, blocks protein elongation very effectively. Hence, HHT can repress the replication of many coronaviruses at the nano-molar concentration. In two mouse models, HHT clears SARS-CoV-2 in 3 days, especially by nasal dripping of 40 ug per day. We also use dogs to confirm the safety of HHT delivered by nebulization. The nebulization scheme could be ready for large-scale applications at the onset of the next epidemics. For the current COVID-19, a clinical trial has been approved by the Ditan hospital of Beijing but could not be implemented for want of patients. The protocol is available to qualified medical facilities.

microbiology↗

bioRxiv2021

A simple micropreparative gel electrophoresis technique for purification of proteins, nucleic acids, and bioconjugates

The biochemical and biomedical fields hinge on the ability to effectively separate and purify biological macromolecules. Though this need is largely addressed with a variety of chromatographic and electrophoretic purification techniques, such techniques are usually laborious, time-consuming, and often require complex and costly instalments that are inaccessible to most laboratories. In this work, we introduce a simple micro-preparative (MP) method based on polyacrylamide gel electrophoresis (PAGE) to purify biological samples containing proteins, nucleic acids, and complex bioconjugates. Using a conventional vertical slab system, we demonstrate the extraction of purified DNA, proteins, and DNA-protein bioconjugates from their respective mixtures using MP-PAGE. We apply this system to recover DNA from a ladder mixture with yields of up to 90%, compared to the 58% yield obtained using specialized commercial devices. We also demonstrate the purification of folded enhanced yellow fluorescence protein (EYFP) from crude cell extract with 90% purity, comparable to purities achieved using a two-step size exclusion and immobilized metal-ion affinity chromatography purification procedure. Finally, we demonstrate the successful isolation of an EYFP-DNA bioconjugate sample that otherwise could not be processed using the two-step chromatography procedure. MP-PAGE thus offers a rapid and versatile means of purifying a variety of biomolecules without the need for specialized equipment.

biochemistry↗

bioRxiv2020

SARS-CoV-2 infection causes transient olfactory dysfunction in mice

Olfactory dysfunction caused by SARS-CoV-2 infection represents as one of the most predictive and common symptoms in COVID-19 patients. However, the causal link between SARS-CoV-2 infection and olfactory disorders remains lacking. Herein we demonstrate intranasal inoculation of SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), resulting in transient olfactory dysfunction in humanized ACE2 mice. The sustentacular cells and Bowmans gland cells in OE were identified as the major targets of SARS-CoV-2 before the invasion into olfactory sensory neurons. Remarkably, SARS-CoV-2 infection triggers cell death and immune cell infiltration, and impairs the uniformity of OE structure. Combined transcriptomic and proteomic analyses reveal the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptors in OE from the infected animals. Overall, our mouse model recapitulates the olfactory dysfunction in COVID-19 patients, and provides critical clues to understand the physiological basis for extrapulmonary manifestations of COVID-19.

microbiology↗