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Engineered ion channel offers precise, non-invasive control of brain activity
Engineered ion channel offers precise, non-invasive control of brain activity

Associated Press

time4 days ago

  • Health
  • Associated Press

Engineered ion channel offers precise, non-invasive control of brain activity

FAYETTEVILLE, GA, UNITED STATES, May 30, 2025 / / -- In a breakthrough advancement for neuroscience, researchers have developed RADICAL, a cutting-edge chemogenetic tool that allows for the precise manipulation of neuronal activity using a synthetic chemical, cyclohexanol ( CHXOL ). Unlike traditional methods that rely on invasive optics or slow-acting G-protein coupled receptors, RADICAL utilizes a modified TRPM8 ion channel to enable rapid and targeted control of calcium influx in neurons. This innovative tool has the potential to advance brain function research and open up new therapeutic possibilities for neurological disorders. Current technologies for controlling neuronal activity—such as optogenetics and chemogenetics—have their limitations. Optogenetics requires invasive light delivery, while chemogenetic systems like DREADDs rely on slow and indirect cellular signaling pathways. Additionally, engineered ligand-gated ion channels, such as those based on nicotinic receptors, can result in unintended interactions with native proteins. These challenges have highlighted the need for a more efficient, non-invasive, and precise method of modulating neuronal excitability. In response to this gap, researchers sought to develop RADICAL, a novel chemogenetic tool that addresses these limitations. In a letter (DOI: 10.1093/procel/pwae048 ) published on September 3, 2024, in Protein & Cell, a team from Zhejiang University unveiled RADICAL, an engineered ion channel activated by cyclohexanol (CHXOL). By introducing specific mutations to the TRPM8 ion channel, they created a system that responds with exceptional sensitivity and specificity to CHXOL. This innovation allows for precise neuronal control without interfering with the brain's native functions, marking a significant step forward in chemogenetics. The key modification in RADICAL was the engineering of the TRPM8 ion channel, which is naturally expressed at low levels in the brain, minimizing potential disruptions to endogenous systems. The team introduced two critical mutations (I846F and I985K) to the TRPM8 ion channel. The I846F mutation restored CHXOL binding, while I985K enhanced voltage sensitivity, enabling robust activation even at hyperpolarizing potentials (-80 mV). Patch-clamp recordings and calcium imaging confirmed the double mutant, TRPM8-I846F-I985K's EC50 of 1.17 mmol/L for CHXOL at depolarizing potentials (+80 mV). In vivo, RADICAL demonstrated its potential: CHXOL administration enhanced fear extinction memory in mice by activating neurons in the infralimbic cortex (IL), and also increased locomotor activity when expressed in astrocytes of the ventral tegmental area (VTA). Importantly, the tool's calcium permeability and minimal cell death risk, as shown in HEK293T cells, suggest its suitability for studying calcium-dependent processes such as learning and memory. Dr. Fan Yang, one of the co-corresponding authors of the study, said: RADICAL represents a major breakthrough in chemogenetics. Its ability to modulate neuronal activity with high precision and minimal off-target effects makes it a versatile tool for both basic neuroscience research and the development of therapeutic interventions. With its non-invasive approach and high specificity, RADICAL has substantial potential in both research and clinical settings. It could enhance our understanding of neurological conditions such as memory disorders, addiction, and mood disorders by providing a precise way to manipulate neuronal circuits. Furthermore, future efforts to miniaturize the tool for adeno-associated virus (AAV) delivery could broaden its applicability in gene therapy. RADICAL's unique combination of speed, specificity, and safety positions it as a powerful platform for next-generation treatments of brain diseases. References DOI 10.1093/procel/pwae048 Original Source URL Funding Information This work was supported by funding from the National Natural Science Foundation of China (32122040 and 31971040 to F.Y.; 32071017 and 31922031 to Y.C.); Zhejiang Provincial Natural Science Foundation of China (LR20C050002 to F.Y.); China Postdoctoral Program for Innovative Talents (BX20230323 to H.Z.); China Postdoctoral Science Foundation (2024M752858 to H.Z.); The Fundamental Research Funds for the Central Universities (226-2022-00227 to F.Y.; 226-2022-00149 to Y.C.); Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions (NYKFKT2019001 to Y.C.); The Fundamental Research Funds for the Central Universities (226-2022-00227 to F.Y.). Lucy Wang BioDesign Research email us here Legal Disclaimer: EIN Presswire provides this news content 'as is' without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

Election battle on Chinese apps intensifies as Liberals target crucial voters
Election battle on Chinese apps intensifies as Liberals target crucial voters

ABC News

time26-04-2025

  • Politics
  • ABC News

Election battle on Chinese apps intensifies as Liberals target crucial voters

An intensifying election battle is unfolding on Chinese social media apps — as the Liberals ramp up efforts to win back a crucial group of voters who abandoned the party at the 2022 election. Researchers monitoring Australian political advertising and campaigning on popular apps WeChat and RedNote have noticed a surge in activity by the major parties and independents in recent weeks. Read more about the federal election: Want even more? Here's where you can find all our 2025 University of Melbourne research fellow Fan Yang said one party appeared to be campaigning particularly heavily on Chinese platforms. "We have seen a higher number of political advertising by Liberal Party members," she told ABC News. Dr Yang is leading the RECapture project, along with Robbie Fordyce from Monash University and Luke Heemsbergen from Deakin University. Since January, the team has found more than 220 authorised Liberal ads on WeChat and about 30 for Labor. Political attack ads have appeared on Chinese social media recently. ( Supplied: RECapture Research Project ) In the past fortnight, the campaign battle on Chinese platforms has escalated, as political attack ads targeting Prime Minister Anthony Albanese and Opposition Leader Peter Dutton — authorised by the major parties — have appeared. Dr Yang said the WeChat battleground had also been evolving in the final weeks of the election campaign. "Just in recent weeks, the candidates have diversified. We're seeing more independents and minor parties," she said. Both major parties seek to win over Chinese-Australian voters. ( Supplied: RECapture Research Project ) Key seats targeted with Chinese social media campaigns The Liberal candidate for the ultra-marginal Sydney seat of Bennelong appears to have one of the largest Chinese social media campaigns. Scott Yung has appeared in more than 100 authorised ads found by the RECapture team since January. Mr Yung is aiming to oust Labor MP Jerome Laxale from the electorate, which is now notionally Liberal due to a boundary redraw. Photo shows A graphic showing a range of reader comments about potential issues in Australia's 2025 federal election. What do you need to know before you vote in the upcoming federal election? What would you ask the candidates? Have Your Say. About 30 per cent of residents in Bennelong have Chinese heritage. It was among a handful of seats lost by the Liberals in 2022 after there were significant swings against the party in areas with large Chinese-Australian communities. An internal review found the backlash was partially driven by the Morrison government's criticisms of the Chinese government and an "incorrect perception" it was also aimed at the wider Chinese community. It recommended "rebuilding the Liberal Party's relationship with the Chinese community" as a priority. Blue-ribbon Bradfield on Sydney's north shore is the electorate with the fifth largest population of Chinese voters in Australia. Candidates for Bradfield and Bennelong have been appearing on Chinese platforms. ( Supplied: RECapture Research Project ) It's also among the seats the Liberal Party is at risk of losing at the upcoming election, as former government minister Paul Fletcher retires. The Liberals' pick for Bradfield, Gisele Kapterian, has appeared in dozens of authorised ads on WeChat this year. Nicolette Boele, the teal independent candidate regarded as Ms Kapterian's toughest competition, has also recently appeared in campaign material on the Chinese platform. A spokesperson for the Liberals declined to comment on the ads appearing on Chinese social media, as it is against the rules of major parties to publicly discuss campaign strategy. "Liberal candidates are communicating with their communities about the important choice they have on May 3," he said. 'Important tool' to speak to community The RECapture project has also been examining campaign material on the Chinese version of Instagram, known as RedNote or Little Red Book. Dr Yang said posts on this platform often differed in tone from content shared on the English-language social media accounts of MPs and candidates. "What I find interesting is some of the content is tailored to Chinese migrant communities — for example, content about Australian politicians going to a Chinese restaurant, drinking bubble teas, going to Asian grocery stores," she said. "This kind of content is not necessarily visible or published on English-language social media services like Instagram, but they're on RedNote to target Chinese-Australian voters." It's harder for politicians to campaign on RedNote — due to the platform discouraging political content and a "shadow ban" preventing a number of MPs and candidates from being found on the app via a name search. Some MPs regularly use Chinese social media to stay in touch with members of their multicultural communities. Dr Yang co-leads the RECapture project. ( ABC News: Peter Healy ) Labor MP Sally Sitou described it as a "really important tool" to communicate directly with the large Chinese community in her inner-west Sydney electorate of Reid. "You wouldn't expect to be speaking to young people through The Australian newspaper — you'd expect to be speaking to them through the channels they use, like Instagram and TikTok," she said. "The same can be said for the Chinese community. They are mostly now on WeChat and Little Red Book (or RedNote), so that's the best way to get in touch with them." The Liberal candidate vying for Ms Sitou's seat, Grange Chung, has also been increasingly active on Chinese social media — including links to the apps on his campaign posters. "We're a very diverse electorate, so I need to reach out to particularly, say, the Chinese community, through the social media they use and we're going through all available channels in that regard," he said in a recent TV interview with ABC News. 'A good way to pass on information' Justin Zhang has lived in Reid for more than a decade, after migrating to Australia from China. The father-of-one, who works in the banking sector, stays up to date using a combination of traditional news services, English-language social media platforms and Chinese apps. Mr Zhang is happy to see more Australian politicians using Chinese social media apps to communicate with migrant communities. ( ABC News: Berge Breiland ) He told the ABC he was glad to see more Australian MPs and political candidates on Chinese platforms. "It's good they're exploring the new social media for new migrants like me," he said. "We use social media a lot." Jack Fang is a Chinese-Australian who lives in the electorate of Bradfield — on Sydney's north shore. He uses both WeChat and RedNote. "The most interesting thing for me is where I can find the best restaurant," he said. "But there is a lot of information relating to elections as well. It's a good way to pass the information on — especially for people where English is not their first language." Loading Having trouble seeing this form? Try

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