Wu T et al. (2023) Cell Res "6mA-METL-9 axis regulates innate immunity in C. elegans."

He C, Wu T

[Cell Res, 2023]

Wu T et al. (2019) Chemosphere "Caenorhabditis elegans as a complete model organism for biosafety assessments of nanoparticles."

Liang X, Tang M, Xu H, Wu T

[Chemosphere, 2019]

The number of biosafety evaluation studies of nanoparticles (NPs) using different biological models is increasing with the rapid development of nanotechnology. Thus far, nematode Caenorhabditis elegans (C.elegans), as a complete model organism, has become an important invivo alternative assay system to assess the risk of NPs, especially at the environmental level. According to results of qualitative and quantitative analyses, it can be concluded that studies of nanoscientific research using C.elegans is persistently growing. However, the comprehensive conclusion and analysis of toxic effects of NPs in C.elegans are limited and chaotic. This review focused on the effects, especially sublethal ones, induced by NPs in C.elegans, including the development, intestinal function, immune response, neuronal function, and reproduction, as well as the underlying mechanisms of NPs causing these effects, including oxidative stress and alterations of several signaling pathways. Furthermore, we presented some factors that influence the toxic effects of NPs in C.elegans. The advantages and limitations of using nematodes in the nanotoxicology study were also discussed. Finally, we predicted that the application of C.elegans to assess long-term impacts of metal oxide NPs in the ecosystem would become a vital part of the nanoscientific research field, which provided an insight for further study.

Wu T et al. (2023) Nature "Pathogenic bacteria modulate pheromone response to promote mating."

Wu T, Gracida X, Duan F, Liu H, Wu M, Chen M, Ge M, Butcher RA, Saltzman AL, Zhang Y, Li C, Dar AR, Yang W, Liang J

[Nature, 2023]

Pathogens generate ubiquitous selective pressures and host-pathogen interactions alter social behaviours in many animals^1-4. However, very little is known about the neuronal mechanisms underlying pathogen-induced changes in social behaviour. Here we show that in adult Caenorhabditis elegans hermaphrodites, exposure to a bacterial pathogen (Pseudomonas aeruginosa) modulates sensory responses to pheromones by inducing the expression of the chemoreceptor STR-44 to promote mating. Under standard conditions, C. elegans hermaphrodites avoid a mixture of ascaroside pheromones to facilitate dispersal^5-13. We find that exposure to the pathogenic Pseudomonas bacteria enables pheromone responses in AWA sensory neurons, which mediate attractive chemotaxis, to suppress the avoidance. Pathogen exposure induces str-44 expression in AWA neurons, a process regulated by a transcription factor zip-5 that also displays a pathogen-induced increase in expression in AWA. STR-44 acts as a pheromone receptor and its function in AWA neurons is required for pathogen-induced AWA pheromone response and suppression of pheromone avoidance. Furthermore, we show that C. elegans hermaphrodites, which reproduce mainly through self-fertilization, increase the rate of mating with males after pathogen exposure and that this increase requires str-44 in AWA neurons. Thus, our results uncover a causal mechanism for pathogen-induced social behaviour plasticity, which can promote genetic diversity and facilitate adaptation of the host animals.

Wu, T. et al. (2017) International Worm Meeting "Dissecting a network of the insulin-like peptides underlying olfactory learning."

Zhang, Y., Caballero, A., Alcedo, J., Choi, M., Katic, I., Regenass, M., Fernandes de Abreu, D., Ch'ng, Q., Wu, T.

[International Worm Meeting, 2017]

Insulin and insulin-like peptides (ILPs) act through conserved signaling pathways to regulate neural plasticity in both invertebrates and vertebrates. The genomes of many animals, including that of the humans, encode multiple ILPs. Our previous studies characterize two C. elegans ILPs that regulate a form of aversive olfactory learning in the nematode. These two ILPs interact with other ILP family members in a transcriptional network (Chen et al., 2013; Fernandes de Abreu et al., 2014). We hypothesize that multiple ILPs act as a network to regulate physiological events, including learning, in response to various contexts. To address this hypothesis, we have examined the learning ability in the deletion mutants of the ILPs in the network. We find that deleting ins-4, ins-8 or ins-35 significantly disrupt the aversive olfactory learning. We show that these ILPs are expressed in different sensory neurons and that the aversive training alters the neuronal expressions. In addition, other types of experience, such as pheromone exposure and starvation, regulate the expression of these ILPs differently. Together, these results support our hypothesis that ILPs regulate learning in an interactive network that responds to the environment and experience in a context-dependent manner.

Wu T et al. (2020) Int J Nanomedicine "The NLRP3-Mediated Neuroinflammatory Responses to CdTe Quantum Dots and the Protection of ZnS Shell."

He K, Liu X, Wang Y, Tang M, Liang X, Kong L, Wu T, Li Y

[Int J Nanomedicine, 2020]

Introduction: Since CdTe quantum dots (QDs) are still widely considered as advanced fluorescent probes because of their far superior optical performance and fluorescence efficiency over non-cadmium QDs, it is important to find ways to control their toxicity. Methods: , the hippocampus of mice, and cultured microglia were measured in order to evaluate the neuroinflammation caused by cadmium-containing QDs and the potential mechanisms. Results: . In the mice treated with QDs, neuroinflammatory responses to QDs in the hippocampus, including microglial activation and IL-1B release, occurred as well. When investigating the mechanisms of cadmium-containing QDs causing IL-1B-mediated inflammation, the findings suggested that cadmium-containing QDsactivated the NLRP3 inflammasome by causing excessive ROS generation, and resulted in IL-1B release. Discussion: Even though the milder immune responses and neurotoxicity of CdTe@ZnS QDs compared with CdTe QDs indicated the protective role of ZnS coating, the inhibitions of NLRP3 expression and ROS production completely reduced the IL-1B-mediated inflammation. This provided valuable information that inhibiting target molecules is an effective and efficient way to alleviate the toxicity of cadmium-containing QDs, so it is important to evaluate QDs through a mechanism-based risk assessment.

Wu T et al. (2019) Neuron "Pheromones Modulate Learning by Regulating the Balanced Signals of Two Insulin-like Peptides."

Caballero A, Yang W, Wu T, Fernandes De Abreu DA, Liu H, Zhang Y, Ch'ng Q, Duan F, Butcher RA, Dar AR, Alcedo J

[Neuron, 2019]

Social environment modulates learning through unknown mechanisms. Here, we report that a pheromone mixture that signals overcrowding inhibits C.elegans from learning to avoid pathogenic bacteria. We find that learning depends on the balanced signaling of two insulin-like peptides (ILPs), INS-16 and INS-4, which act respectively in the pheromone-sensing neuron ADL and the bacteria-sensing neuron AWA. Pheromone exposure inhibits learning by disrupting this balance: it activates ADL and increases expression of ins-16, and this cellular effect reduces AWA activity and AWA-expressed ins-4. The activities of the sensory neurons are required for learning and the expression of the ILPs. Interestingly, pheromones also promote the ingestion of pathogenic bacteria while increasing resistance to the pathogen. Thus, the balance of the ILP signals integrates social information into the learning process as part of a coordinated adaptive response that allows consumption of harmful food during times of high population density.

Wu T et al. (2015) Nanoscale "Two-colour fluorescent imaging in organisms using self-assembled nano-systems of upconverting nanoparticles and molecular switches."

Qin Z, Wu T, Baillie D, Irie M, Morimoto M, Branda NR, Johnsen B

[Nanoscale, 2015]

The water-insolubility of a potentially versatile photoresponsive 'turn-on' fluorescence probe was overcome by incorporating it into a nano-assembly containing an upconverting nanoparticle wrapped in an amphiphilic polymer. The appeal of the nano-system is not only in the ability to turn "on" and "off" the fluorescence from the organic chromophore using UV and visible light, it is in the fact that the nanoparticle acts as a static probe because it emits red and green light when excited by near infrared light, which is not effected by UV and visible light. This dual-functioning emission behaviour was demonstrated in live organisms.

Wu T et al. (2015) Nanoscale "MPA-capped CdTe quantum dots exposure causes neurotoxic effects in nematode Caenorhabditis elegans by affecting the transporters and receptors of glutamate, serotonin and dopamine at the genetic level, or by increasing ROS, or both."

Wu T, He K, Zhang T, Zhang S, Ying J, Tang M, Xue Y, Zhan Q, Ang S

[Nanoscale, 2015]

As quantum dots (QDs) are widely used in biomedical applications, the number of studies focusing on their biological properties is increasing. While several studies have attempted to evaluate the toxicity of QDs towards neural cells, the in vivo toxic effects on the nervous system and the molecular mechanisms are unclear. The aim of the present study was to investigate the neurotoxic effects and the underlying mechanisms of water-soluble cadmium telluride (CdTe) QDs capped with 3-mercaptopropionic acid (MPA) in Caenorhabditis elegans (C. elegans). Our results showed that exposure to MPA-capped CdTe QDs induced behavioral defects, including alterations to body bending, head thrashing, pharyngeal pumping and defecation intervals, as well as impaired learning and memory behavior plasticity, based on chemotaxis or thermotaxis, in a dose-, time- and size-dependent manner. Further investigations suggested that MPA-capped CdTe QDs exposure inhibited the transporters and receptors of glutamate, serotonin and dopamine in C. elegans at the genetic level within 24 h, while opposite results were observed after 72 h. Additionally, excessive reactive oxygen species (ROS) generation was observed in the CdTe QD-treated worms, which confirmed the common nanotoxicity mechanism of oxidative stress damage, and might overcome the increased gene expression of neurotransmitter transporters and receptors in C. elegans induced by long-term QD exposure, resulting in more severe behavioral impairments.

Castillo-Quan JI et al. (2016) Cell "Metformin: Restraining Nucleocytoplasmic Shuttling to Fight Cancer and Aging."

Castillo-Quan JI, Blackwell TK

[Cell, 2016]

In this issue of Cell, Wu etal. employed C.elegans and human cell experiments to identify a pathway through which metformin increases lifespan and inhibits growth. A key transcriptional target, ACAD10, is activated when metformin induces nuclear exclusion of the GTPase RagC, thereby inhibiting mTORC1 through an unexpected mechanism.

Ji Wu et al. (2002) East Coast Worm Meeting "Regulation of Touch Cell Functional Genes"

Ji Wu, Martin Chalfie

[East Coast Worm Meeting, 2002]

We have previously shown that egl-44 and egl-46 are two transcription regulators involved in the development of several types of neurons in C. elegans, with significant homology in other organisms, and that they repress the expression of touch cell-specific features in FLP neurons (Wu et al., 2001,Genes. Dev., 15: 789).