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Kanazawa University research: High speed atomic force microscopy studies provide insights into influenza A viral replication

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KANAZAWA, Japan, July 29, 2024 /PRNewswire/ — Researchers at Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, IMDEA Nanoscience (Madrid, Spain) and CNB-CSIC (Madrid, Spain) report in ACS Nano experiments that reveal a cycle of conformational stages that recombinant Influenza A genomes pass through during RNA synthesis.

Influenza A is a global health risk responsible for local epidemics and deadly pandemics. As such, the mechanism by which the virus replicates itself has attracted significant interest. Researchers led by Shingo Fukuda at Nano Life Science Institute (WPI-NanoLSI) at Kanazawa University in Japan, Jaime Martin-Benito at CNB-CSIC and Borja Ibarra  at IMDEA Nanociencia in Spain, used high-speed atomic force microscopy and electron microscopy to pin down the conformational dynamics of recombinant viral genomes (or rRNPs) during RNA synthesis.

Previous attempts to understand what possible conformational changes occur during Influenza A viral multiplication cycle had been hindered by what the researchers describe as the “bulky double-helical structure” of the viral RNPs (vRNP, Fig.1 A), which made it hard to see what was going on. As a result the researchers produced a circular recombinant ribonucleoprotein complex (rRNP) (Fig.1 B), which allowed them to overcome the ‘bulky issue’. The authors used HS-AFM to follow conformational changes of individual rRNP complexes in real-time during active RNA synthesis (Fig.1 C).

Their work provides first direct experimental evidence showing that individual rRNPs can be recycled for multiple transcription and replication cycles. This is a key feature for viral multiplication. In addition, their study highlights how factors that affect the stability of the secondary structures of the nascent RNA affect the rate of RNA synthesis.

The authors concluded that the approach is useful for investigating viral transcription and replication mechanisms. “Transcriptional pausing is an intrinsic property of most RNA polymerases, and its regulation constitutes one of the central mechanisms of control of gene expression,” they add. “Future single-molecule experiments of real-time RNA synthesis kinetics by the IAV RdRp [influenza A virus RNA dependent RNA polymerase] within the context of the RNP will help to elucidate the nature of putative pause states and their roles in viral transcription and replication.”

Figure

https://nanolsi.kanazawa-u.ac.jp/wp/wp-content/uploads/Figure-1-2.jpg

Caption : Fig.1 (A, B) HS-AFM images of vRNP (A) and rRNP (B). (C) Successive HS-AFM images of rRNP during RNA synthesis. © 2024 Carlero, et al. Published by American Chemical Society

Glossary

RNA synthesis

Ribonucleic acid (RNA) is a polymer and a nucleic acid. Its replication is catalyzed by an enzyme known as RNA polymerase. The synthesis only proceeds in the presence of the nucleotide and proteins required to build up the RNA molecule.

Although RNA synthesis can use DNA as the synthesis template, a number of viruses replicate with RNA as the template. The enzyme that catalyzes this type of synthesis is known as RNA dependent RNA polymerase.

Recombinant ribonucleic proteins

Recombinant ribonucleoproteins are useful for ways of studying RNA processes. In this instance the authors used a recombinant ribonucleoprotein made up of the same protein components but just 352 nucleotides long, where the RNA segment used had been shown to avoid supercoiling.

High-speed atomic force microscopy

This imaging technique uses a nanosized tip at the end of a cantilever that is scanned over a sample. It can be used to determine the topography of a sample surface from the change in the strength of forces between the tip and the sample with distance, and the resulting deflection of the cantilever. It was first developed in the 1980s but a number of modifications have augmented the functionality of the technique since. It is better suited to imaging biological samples than the scanning tunneling microscope that had been developed because it does not require a conducting sample.

In the 2000s Toshio Ando at Kanazawa University was able to improve the scanning speed to such an extent that moving images could be captured. This allowed people to use the technique to visualize molecular processes for the first time.

Reference

Diego Carlero, Shingo Fukuda, Rebeca Bocanegra, Toshio Ando, Jaime Martin-Benito, and Borja Ibarra Conformational Dynamics of Influenza A Virus Ribonucleoprotein Complexes during RNA Synthesis ACS Nano 2024.

DOI：10.1021/acsnano.4c01362

URL: https://pubs.acs.org/doi/10.1021/acsnano.4c01362

Funding acknowledgements

This work was supported by the NanoLSI Visiting Fellows Program 2019 (to B.I.), the World Premier International Research Center Initiative (WPI), MEXT (Japan), and grants PGC2018-099341-B-I00 (to B.I.), PID2021-126755NB-I00 (to B.I.), and PID2020-117752RB-I00 (to J.M.B.) financed by MCIU/AEI/10.13039/501100011033 and FEDER, UE,  Grant TED2021-132748B-I00 financed by the European Union “NextGeneration EU”/PRTR (to J.M.B.), and Grant No. 20K15140 financed by JSPS KAKENHI (to S.F.). IMDEA Nanociencia acknowledges support from the Severo Ochoa Program for Centers of Excellence in R&D (CEX2020-001039-S).

Contact

Hiroe Yoneda (Ms)
Senior Specialist in Project Planning and Outreach
NanoLSI Administration Office, Nano Life Science Institute (WPI-NanoLSI)
Kanazawa University
Kakuma-machi, Kanazawa 920-1192, Japan
Email: nanolsi-office@adm.kanazawa-u.ac.jp
Tel: +81 (76) 234-4555

About Nano Life Science Institute (WPI-NanoLSI), Kanazawa University

Understanding nanoscale mechanisms of life phenomena by exploring “uncharted nano-realms”

Cells are the basic units of almost all life forms. We are developing nanoprobe technologies that allow direct imaging, analysis, and manipulation of the behavior and dynamics of important macromolecules in living organisms, such as proteins and nucleic acids, at the surface and interior of cells. We aim at acquiring a fundamental understanding of the various life phenomena at the nanoscale.

https://nanolsi.kanazawa-u.ac.jp/en/

About the World Premier International Research Center Initiative (WPI)

The WPI program was launched in 2007 by Japan’s Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS).

See the latest research news from the centers at the WPI News Portal: https://www.eurekalert.org/newsportal/WPI

Main WPI program site: 

www.jsps.go.jp/english/e-toplevel

About Kanazawa University

As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities.

The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas.

http://www.kanazawa-u.ac.jp/en/

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SOFTSWISS Presents Three Innovative Products in South Africa

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September 30, 2024

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GZIRA, Malta, Sept. 30, 2024 /PRNewswire/ — SOFTSWISS, a global tech expert with over 15 years of experience in iGaming, has presented three new products made in collaboration with Turfsport, a leading South African software provider, recently acquired by the company.

Lotto Software
The online lottery market is projected to generate over $16.9 billion in revenue in 2024 and reach over $22.0 billion by 2029. The new Lotto Software enables operators to offer a wide range of lottery draw betting options independent of traditional lottery organisers.

The solution handles up to 80 bets and processes 3,333 bet results per second covering over 300 lottery draws worldwide. It provides an intuitive betting experience, offering numbers, sum, count, positions, colours, even/odd, and jackpot-type draws. The platform seamlessly integrates with external wallet connections without additional software. In-house lottery feed ensures fraud prevention through dual-source validation and advanced web scraping technologies.

Retail Betting Solution
The global sports betting and lotteries market is rebounding post-pandemic, with industry revenue estimated at $243.7 billion in 2024. The Retail Betting Solution, supporting betting on sports, horse racing, lottery draws, and casino games, empowers operators to establish offline gambling businesses swiftly and legally.

The solution allows players to manage their accounts across channels by connecting retail and online platforms. Operators can set up various shop configurations and track profits with a comprehensive cash management tool. The Retail Betting Solution offers pre-match and live event feeds and casino games from multiple providers at dedicated kiosks.

Horse Racing Module
The global horse betting market is expected to reach $91.2 billion by 2032, registering a CAGR of 7.6% from 2023 to 2032. The new Horse Racing Module integrated into the SOFTSWISS Sportsbook, enriches the betting portfolio by allowing players to place fixed-odds bets on multiple markets.

The Horse Racing Module provides operators with additional business opportunities, covering over 2,400 international and local races monthly. The solution engages players with race cards, silks, and multiple bet types and offers operators unique skins and configurations to align with various brand identities.

Max Trafimovich, CCO at SOFTSWISS, shares: “We present a product portfolio that not only meets the growing demand for diverse and engaging betting options but also equips our clients with an effective tool to grow their businesses. With these new solutions, operators can now offer their players a unique, reliable, and enjoyable experience.”

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Viet Nam Inaugurates Center for the Fourth Industrial Revolution during Ho Chi Minh City Economic Forum

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September 30, 2024

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HO CHI MINH CITY, Vietnam, Sept. 30, 2024 /PRNewswire/ — Ho Chi Minh City, a leading center for economic, technological, and scientific development and international gateway of Viet Nam, recently hosted the 5th Ho Chi Minh City Economic Forum (HEF 2024) from September 24-27. The Forum focused on “Industrial Transformation: A New Growth Driver for Sustainable Development in Ho Chi Minh City” and culminated with the inauguration of the Center for the Fourth Industrial Revolution (C4IR) in Ho Chi Minh City.

The event welcomed nearly 1,500 delegates, including Viet Nam’s Prime Minister Pham Minh Chinh, government representatives, local leaders, international organizations, experts, and businesses from countries, such as the United States, China, Japan, South Korea and across Europe.

During the Policy Dialogue, Prime Minister Pham Minh Chinh emphasized “The industrial transformation in Ho Chi Minh City must be comprehensive, tied closely to the ambition of building a smart city with smart governance. Thus, The City will need to have special independent policies to accelerate industrial transformation.”

Ho Chi Minh City has already implemented strategies focused on the green economy, digital transformation for businesses, and favorable policies for startups and innovation. City leaders announced their commitment to further accelerate efforts in twin transformation (green hand in hand with digital) and expanding cooperation with international organizations, such as the World Bank and the Fourth Industrial Revolution Center Network of the World Economic Forum. A key focus will be establishing a modern civil service system with incentives to enhance policy implementation.

The inauguration of C4IR marks a significant milestone in the cooperation between the Vietnamese government and the World Economic Forum period 2023-2026. As the second C4IR in Southeast Asia and the 19th globally, C4IR Ho Chi Minh City will serve as a key hub for the WEF, connecting Viet Nam with global experts to drive industrial transformation.

After five editions of the Ho Chi Minh City Economic Forum, The City is ready to shape the Forum into an independent organization that will support the City’s socio-economic development goals. HEF 2024 followed the 2nd Ho Chi Minh City Friendship Dialogue (September 23-24), themed “Industrial Transformation: Experiences and Priorities in Development Cooperation,” aimed to strengthen cooperative relationships between Ho Chi Minh City and its sister cities worldwide, while promoting Vietnamese culture and people.

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UST to Expand India Presence with State-of-the-art Kochi Campus and Create Over 3,000 New Jobs in the Next 5 Years

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September 30, 2024

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Laid Foundation Stone for Own Campus at Kochi Infopark, Kochi Phase 2; To be the second owned campus in India for UST after Thiruvananthapuram.

KOCHI, India, Sept. 30, 2024 /PRNewswire/ — UST, a leading digital transformation solutions company, announced plans to expand its presence in India by adding over 3000 new jobs at its upcoming Kochi campus in the next five years, as it gets ready to inaugurate its own campus in Kochi, Kerala, by December 2027. The company, which has set itself a target of 6,000 employees in the next five years, currently employs more than 2,800 people in its existing facility at Infopark Kochi.

The foundation stone for its new Kochi campus that will come up in a sprawling 9-acre land at Infopark Kochi Phase 2, was laid, by Krishna Sudheendra, Chief Executive Officer, UST. Susanth Kurunthil, CEO, Infopark Kochi; Alexander Varghese, Chief Operating Officer, UST; Sunil Balakrishnan, Chief Values Officer & Kochi Center Head, UST; Anil Pillai, Vice President, Campus Development Team, UST, Shilpa Menon, UST Thiruvananthapuram Center Head; Sheffi Anwar, General Manager – Business Operations & Workforce Management, UST; and other leaders and employees, were present.              

The new UST campus in Kochi, which will be completed in three years, will be a 10-floor building and 4400 seats, with an area of over 6,00,000 sq. ft.  The new building will also have a modern gym for employees, and an auditorium with a seating capacity of 1400 seats. The new UST campus building will be built incorporating the latest technology, and energy efficient measures generating green energy. When the Kochi campus goes on stream, it will become the second owned campus in India for UST after Thiruvananthapuram.

UST, which already has a facility operating out of Infopark Kochi, currently caters to US, UK and APAC clients from almost all domains such as healthcare, retail, telecom, financial services/asset management, and hi-tech. Speaking after laying the foundation stone for the new campus building, Krishna Sudheendra, CEO, UST, said that the new campus will not only strengthen UST’s presence in the region but also attract more clients and create new work opportunities, positioning Kochi as a dynamic hub for innovation and growth.

“I congratulate and wish the best to UST in building its own campus at Infopark. The company has shown high levels of commitment and determination in setting this goal of having its own state-of-the-art space in the industrial hub of Kerala, and the results will soon show off,” said Susanth Kurunthil, Chief Executive Officer, Infopark Kochi.

Alexander Varghese, Chief Operating Officer, UST, spoke high of the state-of-the-art infrastructure planned for the campus and appreciated the architecture company’s role in shaping its vision. “Ever since UST began its Kochi operations in 2007, we have been able to post steady growth. The strategic location of Kochi aids companies to easily connect and reach out to other IT locations in South India. This aspect, along with Kochi’s development in social and physical infrastructure arenas, has helped UST attract talent from other locations. With UST’s own campus coming up in Kochi, we will be able to add jobs and customers in a big way,” Alexander Varghese added.

Kochi has built a name as the industrial capital of Kerala. Kochi boasts of advanced infrastructure, a large and highly skilled workforce, and a supportive business environment. With the aim of having its own campus in the city, UST had started the pre-construction work before Covid-19 pandemic.

Sunil Balakrishnan, Chief Values Officer & Kochi Center Head, UST, who expressed pride in the project’s progress, also spoke about the challenges that had arisen, and how the company had overcome all hassles to stay firmly in track. Anil Pillai, Vice President, Campus Development Team, UST, unveiled the new campus design for Kochi Center at the event.

Founded in 1999, UST, which began its India operations with its headquarters in Thiruvananthapuram, has expanded its presence across India with offices in Hyderabad, Kochi, Bengaluru, Pune, Chennai, Coimbatore, Delhi NCR, Ahmedabad, and Hosur.

About UST

Since 1999, UST has worked side by side with the world’s best companies to make a powerful impact through transformation. Powered by technology, inspired by people, and led by our purpose, we partner with our clients from design to operation. Our digital solutions, proprietary platforms, engineering expertise, and innovation ecosystem turn core challenges into impactful, disruptive solutions. With deep industry knowledge and a future-ready mindset, we infuse innovation and agility into our clients’ organizations—delivering measurable value and positive lasting change for them, their customers, and communities around the world. Together, with 30,000+ employees in 30+ countries, we build for boundless impact—touching billions of lives in the process. Visit us at www.UST.com

Media Contacts, UST:

Tinu Cherian Abraham
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Merrick Laravea
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