The National University of Singapore’s Associate Professor Gary Tan employs technology to model and forecast human movement and then uses that information to optimise evacuation, reduce accidents, and ease traffic congestion during emergency situations. He is particularly interested in modelling how people would run or flee in such circumstances.

According to Associate Professor Gary, when people are in a panic, they act extremely differently and try to anticipate what would happen when, for example, they must evacuate an MRT station due to a bomb threat or a fire.

“In a crisis, each second is crucial. Effective evacuation and rescue plans are essential because delays might result in more fatalities,” says Associate Professor Gary.

Associate Professor Gary together and his students PhD candidates Wang Chengxin and Muhammad Shalihin bin Othman have created this special framework. It uses deep learning methods to track the real-life movement of pedestrians through video feeds. This behaviour is then converted into information that a virtual simulator can use to recreate situations and occurrences that would be too expensive or risky to actually recreate.

The project’s main goal was to create a disaster simulation. This data-driven approach makes it easier to build crowd management tactics that are more effective and delivers a more accurate prediction of human reactions in a crisis.

The framework interprets the movement patterns of pedestrians in real-world video feeds and converts them into data that can be used in a virtual simulator. The technology uses deep learning techniques to identify objects in specific video frames and accurately track them across the video feed.

They recreate settings and imitate actions that would be too expensive or risky to be carried out in real life. This enables the researchers to simulate various evacuation and rescue plans to determine the best course of action to take in an emergency.

The methodology is distinctive because, in contrast to earlier pedestrian simulation methods, it takes a data-driven approach and aims to investigate human behaviour directly from real-life footage. Since they are adapted from real video, this raises the level of realism.

The tracking algorithm that analyses how people move in the films underwent considerable improvement by the researchers. To extract realistic trajectories from real-world recordings, a good tracking algorithm is necessary. They can simulate realistic human movements using highly accurate trajectory data, which enables them to make more accurate predictions.

Following testing, it was discovered that “greater than expected” numbers of trajectories were successfully imported into the simulator from the movies.

Since releasing their research, the team has focused on developing further pedestrian monitoring systems. One, known as the Graph-based Temporal Convolutional Network (GraphTCN), uses artificial intelligence to track pedestrians’ temporal and geographical interactions with one another. The outcome is a behavioural model that can more faithfully simulate human movement.

The researchers are currently developing a new model that thinks more deeply. The Conscious Movement Model, or CMM, analyses CCTV footage and other real-world recordings to identify human behavioural patterns. These patterns are used to build a deep learning model that would subsequently affect the motions of a pedestrian in the simulation.

Researchers can increase the precision of prediction simulations by including genuine pedestrian movements. This will enable them to automatically run optimization algorithms and suggest the optimal course of action in various what-if scenarios. The research can be used to model the movement of both humans and autos in simulations of traffic congestion and accidents in addition to disaster situations.

A Memorandum of Agreement (MoA) was recently signed between Advanced Science and Technology Institute (ASTI) and the Science and Technology Information Institute (STII) to assist remote education in disadvantaged and unserved communities. Both agencies were under the auspices of the Department of Science and Technology (DOST).

According to Franz de Leon, Director, DOST-ASTI, “By strengthening our relationship, we are taking another important step toward achieving our common aim of improving the state of infrastructure, education, resilience, and general quality of life in the country.”

The project known as Resilient Education Information Infrastructure for the New Normal (REIINN) focuses on creating infrastructures and application frameworks to enable the move to remote learning and reduce the nation’s digital divide. The project currently offers two programmes, LokaLTE and RuralCasting.

While RuralCasting creates computer systems that provide educational content to homes via digital TV channels, LokaLTE creates and implements community LTE Networks in rural locations. The collaboration illustrates the DOST’s dedication to using technology-based interventions to connect and provide information to geographically separated schools and communities.

STARBOOKS intends to offer science, technology, and innovation-based content in a variety of forms to children in rural and underserved regions across the nation. It includes millions of digitised science and technology resources in several formats, including text and video/audio, organised in specifically created “pods” with an easy-to-use interface.

Through the DOST’s ASTI and STII collaboration, STARBOOKS, according to Alan Taule, Project Leader, will be able to reach more people, notably students, and eventually, nobody will be left behind in the knowledge divide.

Due to the pandemic, the way education is delivered in the nation has undergone significant change. Teaching had to be done remotely using modular and digital platforms because both public and private schools had to be shuttered to safeguard the health of students and teachers.

To improve the use of blended learning in difficult-to-reach locations, the Department of Education (DepEd) has given several instructional resources to beneficiary schools, students, and staff. Over 8.5 million students have been enrolled by the department for the school year 2021–2022. To promote learning continuity, DepEd has used online and technologically based distance learning approaches such as using TV, radio, printed modules, and online/offline sites, among others.

The department has monitored and provided e-learning gadgets to school beneficiaries aiming to utilise and maximise the benefits of having digital technology to increase access to basic education for all students, particularly those who attend “Last-Mile Schools.”

In addition, many universities and colleges have also used flexible learning systems that were set up by the Commission on Higher Education (CHED). In these kinds of systems, people think about how the learning environment changed during and after the pandemic.

Students could choose their own ways to learn, such as online which uses online classrooms to educate; offline, which uses digital media or printed modules to demonstrate; or blended, which uses both online and offline methods.

Furthermore, through online learning platforms, the Philippines has switched from traditional classroom instruction to online learning. The government has endorsed mobile learning as an effective means for students to continue their education.

Online learning systems have been able to thrive in the country, thus students have access to the available resources in a variety of settings, including blended learning and home education. Any of these modalities are integrated into blended learning to leverage their advantages and produce high-quality education.

The ICT market in Singapore is among the most developed in the world, and its people are among the most technologically savvy. It continues to investigate innovation frontiers like artificial intelligence (AI), cloud/quantum computing, data analytics, and other technologies that could aid its digital economy.

The country has built a top-tier, globally competitive technology sector and encourages the young ones, especially the children to be involved in tech-related activities that could ignite a lifetime interest in any technological programme. With this, GovTech Singapore has promoted some tech activities to keep the young ones entertained -a good investment for their time and effort.

Although coding expertise is in high demand right now on the job market, it’s not all work and no play. For kids of various ages, there are numerous learning facilities offering coding training. Even better, there is a lot of free educational content available online.

The Singapore Science Centre offers opportunities for parents and kids to operate drones and rovers alike. The kids’ ability to pilot over a variety of obstacles in a specially built arena that combines indoor and outdoor aspects will be tested at the Drone-Rover area.

It’s another thing to comprehend how 3D printing works and how this technology can be used in a variety of medical settings. The Science Centre offers a wide variety of 3D printing workshops, but before signing up, make sure to ask the organiser whether there is a minimum age requirement. This is because 3D printing uses machinery that needs to be handled carefully.

investigating robotic arms that can solve Rubik’s cubes and dance when programmed. Beyond robots, the Smart Nation Playscape includes other toys. Get a thorough tech immersion with exhibitions covering, among other things, biometrics, blockchain, AI, sensors, geospatial technology, and user experience.

Children can discover how technology is increasingly driving daily city life after being awed by the model buildings forming a miniature rendering of Singapore’s landscape at the Smart Nation Cityscape, including supporting the planning of towns and amenities and being embedded in the infrastructure.

For the public to learn more about Singapore’s tech projects and digital government services, a 12m long truck equipped with interactive game stations is being used as part of the Smart Nation Builder travelling roadshow.

SPF Anti-Scam Games: ‘Scambat’ and ‘Scam Me If You Can’

The Singapore Police Force (SPF) is always looking for novel approaches to educate the public about fraud. Recently, they introduced two new games tag as “ScamBat” and “Scam Me If You Can,” which are meant to increase their touchpoints and effectively build the bonds between SPF and the public, notably the younger generations, through engaging and educational activities.

“ScamBat” was created in collaboration with students from Singapore Polytechnic’s Media, Arts & Design School. It is an analogue card game for many players that exposes participants to various scams. All elementary, secondary, and tertiary schools, polytechnics, and universities will receive copies across the entire island.

Through the planned physical outreach and engagement initiatives of the Neighbourhood Police Centres (NPCs), the public will also obtain the “ScamBat” set.

On “Scam Me If You Can,” on the other hand, is a five-minute single-player game played on a mobile touchscreen kiosk. Players can power up by taking anti-scam quizzes while they swipe to match tiles and earn points. Players have a chance to win a secret prize from the machine after passing the tests.

For a month, SPF will simultaneously deploy two kiosks in two distinct public areas with substantial foot traffic before moving to the following two places.

City University of Hong Kong (CityU) signed Memoranda of Understanding (MoUs) with three venture capital funds and technology companies to establish a co-investment partnership that will provide at least HK$ 15 million in additional angel fund investment each year to selected start-ups incubated by CityU’s large-scale innovation and entrepreneurship programme, HK Tech 300. This joint effort supports start-ups that specifically benefit social and environmental sustainability and promotes the development of innovation and technology in Hong Kong.

The venture capital funds and technology companies are a company specialising in driving investment for bringing positive impacts to society and the environment; a technology enterprise specialising in the development of virtual reality and augmented reality, interactive solution services, and metaverse-related technology; and a professional service provider and business incubator. These three companies will each invest at least HK$5 million in the first year after signing the MoU and provide co-investment to selected start-ups together with the HK Tech 300 Angel Fund.

In his speech at the signing ceremony, the Under Secretary for Innovation and Technology at HKSAR, who witnessed the ceremony stated that said HK Tech 300 had been well received since its launch. In just over a year, it had already yielded fruitful results and become a new driving force for the innovation and technology ecosystem in Hong Kong. He believes the additional funding from a variety of enterprises and venture capital funds in the innovation and technology circle with actual investment in HK Tech 300 will vitalise the development of innovation and technology in Hong Kong.

The CityU Council Member and Board Chairman of CityU Enterprises Limited noted that CityU has been working closely with the innovation and technology sector to build a bridge between HK Tech 300 start-ups and industry to create a more complete runway for their development. He added that the University looks forward to working with more industry leaders and investors in the future to assist more outstanding start-ups, and promote the development of innovation and technology in Hong Kong and beyond.

The Director & CTO of the company specialising in driving investment for bringing positive impacts to society and the environment noted that through this partnership with CityU start-ups can be supported to leverage technology and spur sustainable development in Hong Kong.

The Executive Director of the tech firm that specialises in the development of VR and AR and related technologies hopes to share their experience and resources with more start-ups through this partnership to help them to grow and to motivate other small and medium enterprises to contribute together to the innovative technology industry in Hong Kong, in so doing build a better and more united innovative technology ecosystem. It is hoped that through partnership, more young entrepreneurs can be nurtured.

HK Tech 300 is a large-scale flagship innovation and entrepreneurship programme launched by CityU, under the theme “Venture Beyond Boundaries”. It was designed for aspiring entrepreneurs among CityU students, alumni, research staff and others to establish start-ups and foster their entrepreneurship journey.

HK$500-million-programme offers comprehensive support for entrepreneurship training, a seed fund of HK$100,000 per team, an angel fund of up to HK$1 million per company, co-working space, and networking opportunities in the industrial and commercial communities.

The programme aims to create 300 start-ups in three years, providing educational and growth opportunities for young entrepreneurs and translating CityU research results and intellectual property into practical applications.

For the first time, the researchers used agent-based simulation in Lake Erie to depict the behaviour of blue-green algae in their new modelling study. On the computer, each blue-green alga is represented as an individual, behaving slightly differently depending on its assumed life history.

“The big advance here was to integrate our understanding of the microbiology of the blooms into predictive models,” says Gregory Dick, an environmental microbiologist at the University of Michigan and study co-author. He added that the findings suggest that biologically informed models can reproduce emergent properties of blooms that traditional models cannot predict.

The simulation shows that lowering phosphorus levels to control harmful algal blooms in places like Lake Erie is beneficial to toxic cyanobacteria strains, which can lead to an increase in toxins in the water. Lake Erie is the fourth largest of North America’s five Great Lakes and the eleventh largest lake in the world.

When cyanobacteria, also known as blue-green algae, die, they can produce toxins and deplete lakes of oxygen. Phosphorus is an important nutrient for these algae, and efforts are being made around the world to reduce phosphorus levels and inhibit cyanobacterial growth.

However, as the total number of cyanobacteria decreases, the remaining cyanobacteria have a greater supply of another important nutrient which is nitrogen. Furthermore, higher nitrogen concentrations promote the production of a toxin that protects cyanobacteria from oxidative damage.

The researchers used an agent-based model to simulate how cyanobacteria behave in Lake Erie. They advocate for a paradigm shift in water management, as well as the adoption of a strategy that reduces not only phosphorus but also nitrogen loading in bodies of water.

Cyanobacteria can be harmful to both pets and humans. Due to contaminated drinking water, nearly 500,000 people in the Toledo area were without tap water for nearly three days in August 2014. This is because microcystis, a type of blue-green algae, had produced particularly high levels of the liver toxin microcystin (MC) in Lake Erie.

According to Ferdi Hellweger, chair of Water Quality Engineering at TU Berlin’s Institute of Environmental Technology and lead author, while microcystin is a strong toxin for humans and animals, it is extremely beneficial to cyanobacteria.

Microcystin can occupy specific sites on enzymes that are essential for bacterial life processes. It protects the bacteria from aggressive hydrogen peroxide, which would otherwise attack these binding sites, oxidise the enzymes, and render them ineffective.

Because phosphorus is a nutrient that is only available to a limited extent in nature for bacteria, previous efforts have focused on reducing the use of phosphates as fertilisers in agriculture and reducing the phosphorus content of wastewater through tertiary treatment of wastewater to slow the growth of blue-green algae, even in larger bodies of water like Lake Erie.

Furthermore, a blue-green alga, for example, that was frequently at the water’s surface would have been particularly exposed to sunlight and thus hydrogen peroxide. This increases the chances that it will fully utilise its microcystin production capabilities.

Sunlight can also activate the gene responsible to produce microcystin. Because more light can penetrate to greater depths and stimulate production, this mechanism contributes to the fact that less biomass leads to more toxins.

For their simulation, the researchers used the blue-green alga Microcystis and Lake Erie as the model organism and environment, respectively. The National Oceanic and Atmospheric Administration, the National Institute of Environmental Health Sciences, and the National Science Foundation all contributed to the research.

The Australian National University (ANU) will play a vital role in the research and development of cheaper, more efficient and more sustainable solar technologies as a result of a multi-million-dollar investment that will ignite a spark in Australian solar innovation.

The Albanese government recently announced the Australian Centre for Advanced Photovoltaics (ACAP), led by The University of New South Wales (UNSW) in collaboration with ANU and other institutions, will receive $45 million over the next eight years to ensure the nation continues to be a world leader in the development and deployment of cutting-edge solar technology, including the next iteration of solar panels.

Professor Andrew Blakers, an ANU scholar who coordinates the University’s involvement with ACAP, noted that Australia has a history of delivering creative solutions to further the capabilities of solar photovoltaics (PV) – technology that converts sunlight into electricity – both at home and abroad. This means that the nation is well-positioned to rise to the challenge of developing more capable and more efficient solar cells.

The investment will ensure Australia remains at the forefront of solar innovation globally and will also bring it a step closer to becoming a renewable energy superpower, he said.

Australia generates roughly twice as much solar energy per capita in comparison to any other country. Australia’s main electricity grid currently procures approximately 30 per cent of its electricity from solar and wind, and South Australia procures 70 per cent.

If nations around the world, including Australia, are to meet and surpass current-day modest emissions reduction targets, cost-effective, more efficient and widely accessible solar panels must be developed.

Professor Blakers stated that solar electricity already costs less than electricity from fossil fuels. However, the cost reductions are nowhere near finished. He said that clean and cheap solar and wind electricity allows clean electrification of transport, heating and industry and hence the removal of 80 per cent of greenhouse emissions.

Continued investment and advances in clean energy infrastructure are now, more than ever, necessary amid constraints on the global energy market and higher prices fuelled by ongoing supply issues.

Solving current energy difficulties means greater investment in solar and wind, supplemented by extra transmission to bring the new solar and wind power to the cities.

ACAP is funded by the Australian Renewable Energy Agency (ARENA) and is a collaboration between multiple Australian universities, solar cell production companies, and CSIRO as well as international partners.

The Incoming ACAP Director, Professor Renate Egan from UNSW stated, “We’re looking forward to working with ARENA to deliver low-cost solar technologies through ongoing research. Australia has been leading the world in solar technology development, and there’s still so much more to do. And we’re only just beginning.”

The global solar power market size was US$170.55 billion in 2020. The impact COVID-19 pandemic has been sudden and staggering resulting in the solar power market witnessing a negative demand shock across all regions amid the pandemic.

Recent research notes that this market is expected to grow from US$184.03 billion in 2021 to US$293.18 billion in 2028 at a CAGR of 6.9% during the forecast period. The rapid rise in CAGR is attributable to this market’s demand and growth returning to pre-pandemic levels once the pandemic is over.

While digital fluency enables organisations to leverage intelligent technology to solve increasingly complex challenges, a gap has emerged between innovation and having the right people to drive it. Without a doubt, it is not easy to align digital tools and human resources when technology advances so quickly, creating a disparity that is prevalent at every level of the workforce and in practically every tech function.

From entry-level personnel to experts, getting the right people, with the right skill sets at the right time is a huge challenge. With a limited pool, competitors jostle to onboard skilled, experienced talent disrupting operations and hindering progress.

In an exclusive interview with Mohit Sagar, Group Managing Director and Editor-in-Chief, OpenGov Asia, Tengku Intan Narqiah Tengku Othman, Chief Digital and Information Officer, Group Digitalisation and Information Technology, Sirim Berhad, Malaysia shared her insights on countries struggle to have the right technology and talent in an increasingly digital landscape.

Building a digital talent strategy

Since the outbreak of the pandemic, businesses throughout Malaysia have had to deal with the economic consequences of physical separation and lockdown measures. But, if there is one key takeaway, it is that digital technology adoption is no longer optional for businesses.

Because of the host of restrictions and challenges it brought, the pandemic has accelerated the digitalisation of front-end business processes such as digital marketing and e-commerce.

“I don’t see technology adoption as a one-off project or whether there is a pre, during and post-pandemic. All through my career, whether working in a multinational company or for the government, we have always been involved in technology adoption. If there is business evolution, and there is business, I have yet to find the full stop,” Tengku Intan claims emphatically.

For digital transformation to happen, people need to learn how to use new technologies and the workforce needs to be encouraged to use their skills to make new things happen. They need to think digitally, and they need skills as well.

Employees who learn to think as digital natives do better at their jobs, are happier at work and are more likely to get promoted, she feels.

According to Tengku Intan, to attract, retain and develop digital talent in different industries, the private or public sectors need to meet employee ambition and provide them with technical challenges. Second, employers need to understand the unique talents of their employees and create avenues where they can unleash their potential. Thirdly, if employers cannot match competitive remuneration packages, they need to find ways and means to reward and motivate employees in other ways.

“I don’t think there is one formula that fits all as the culture varied from one organisation to another, and this is a journey where you cannot see the results immediately. But to drive a technology-oriented culture and digital mindset, it has to come from the top,” Tengku Intan is firmly convinced.

The digital mindset in different sectors

A digital mindset is a set of attitudes and behaviours that help people and organisations see how data, algorithms and AI open new opportunities and find ways to succeed in a business world where data-intensive and smart technologies are becoming more important.

According to her, having a pessimistic mindset is the greatest challenge in upskilling employees and imparting digital literacy across the public sector. “I cannot upskill a person who can come up with a million reasons on how not to do it. But to be fair, I cannot ask a fish to fly. As a leader, I need to really understand team members’ talent and upskill them appropriately, and not have them blindly obey orders.”

Digital transitions are often significant, involving changes in shared values, traditions, attitudes and behaviours. Starting with an activity that captures attention and conveys to everyone in the company that a new path is needed is a smart approach.

Tengku Intan says technologies like cloud computing and robotic process automation (RPA) were created to improve company processes rather than to decrease human participation or threat.

“For example, the establishment of cloud computing in SIRIM. The fact that we still retain the current team and reskill them to learn cloud management, instead of installing a physical server, shows we still need people. But tech allows us to improve tremendously on business process, where we no longer required 8 weeks to get one server up, but within 15mins,” Tengku Intan explains.

She acknowledges that knowing how to work effectively not only with people but also with machines, is an important part of collaboration in the digital age. Accepting change is the final requirement for developing a digital mindset.

SIRIM towards a new norm

SIRIM Berhad, is a Malaysian government-owned corporation, an agency under the purview of the Ministry of International Trade and Industry (MITI). It is designated as the mechanism for research and technology development, as well as the national champion of quality with over four decades of experience and knowledge.

SIRIM has always been essential in the growth of Malaysia’s private sector. Utilising its skills and knowledge base, it concentrates on developing new technologies and enhancing the manufacturing, technology and services industries.

The organisation fosters the growth of Small and Medium-Sized Businesses (SMBs) by providing solutions for technology penetration and upgrade, making them an ideal technology partner for SMBs.

“I love the fact that with the current readily available technology we can democratise the application development, data visualisation and analytics work,” Tengku Intan points out.

To drive a digital mindset, SIRIM introduced a hackathon – SIRIM Hack – where non-IT employees learned how to develop simple apps or automate their paper-based forms within 2 days. It was exciting to see some participants develop much better automation than people from an actual IT team.

SIRIM is the best partner for innovation because of its unique advantages in research and technology innovation, industry standards, and quality. They have enabled Malaysian products and services to gain international recognition for their quality and innovation.

Tengku Intan wishes to share lessons learned from her 27-year career in a variety of IT/digital and business fields with the younger generation. “I have only one mantra – Always Hack Yourself!”

She emphasises that people must continue to push themselves as only they know what motivates them. In a working environment, the younger generation should learn how to:

Male-dominated industries and occupations are especially prone to reinforcing harmful stereotypes and creating unfavourable environments that make it even more difficult for women to succeed. Despite other challenges, Tengku Intan made it to the top. “For me, so far, I have not faced any gender discrimination to be where I am today. I worked as hard and as fast as the men. My passion resonates with the energy that was released. And I continuously learn.”

Tengku Intan, however, observes some inequalities, particularly stereotyping women leaders as emotional leaders as opposed to men leaders. Those “emotional leaders” have evolved into empathetic leaders. “And it’s true, you can’t be an empathetic leader if you don’t have a lot of emotions for your people.”

Many ask Tengku Intan what her secret is to successfully balance being a wife and mother of four in a world where technology pervades almost every aspect of people’s lives. She smiles and says, “I have a very supportive and understanding husband. We share and can talk about everything.”

She agrees that this is not the case for many Malaysian working mothers, but she reminds them that it is okay if they have not excelled in their careers; if they want to be committed to being full-time mothers, they should do so.

“I have witnessed many technology women, who choose not to climb the corporate ladder but her dedication and commitment to work are second to none. They are happy to continue where they are. And I believe they are more successful than I am,” Tengku Intan happily recalls.

She is optimistic about the future for Malaysia and is wholeheartedly committed to ensuring quality and equality in Malaysia’s digital journey.

A research team from the LKS Faculty of Medicine at The University of Hong Kong (HKUMed) has developed more efficient CRISPR-Cas9 variants that could be useful for gene therapy applications. By establishing a new pipeline methodology that implements machine learning on high-throughput screening to accurately predict the activity of protein variants, the team has expanded the capacity to analyse up to 20 times more variants at once without needing to acquire additional experimental data, which vastly accelerates the speed in protein engineering.

The pipeline has been successfully applied in several Cas9 optimisations and engineered new Staphylococcus aureus Cas9 (SaCas9) variants with enhanced gene editing efficiency. The findings are now published in Nature Communications and a patent application has been filed based on this work.

Staphylococcus aureus Cas9 (SaCas9) is an ideal candidate for in vivo gene therapy owing to its small size that allows packaging into adeno-associated viral vectors to be delivered into human cells for therapeutic applications. However, its gene-editing activity could be insufficient for some specific disease loci.

Before it can be used as a reliable tool for the treatment of human diseases, further optimisations of SaCas9 are vital within precision medicine. These optimisations must comprise the boosting of its efficiency and precision by altering the Cas9 protein.

The standard protocol for modifying the protein involves saturation mutagenesis, where the number of possible modifications that could be introduced to the protein far exceeds the experimental screening capacity of even the state-of-art high-throughput platforms by order of magnitude.

In their work, the team explored whether combining machine learning with structure-guided mutagenesis library screening could enable the virtual screening of many more modifications to accurately identify the rare and better-performing variants for further in-depth validations.

The machine learning framework was tested on several previously published mutagenesis screens on Cas9 variants and the team was able to show that machine learning could robustly identify the best performing variants by using merely 5-20% of the experimentally determined data.

The Cas9 protein contains several parts, including protospacer adjacent motif (PAM)-interacting (PI) and Wedge (WED) domains to facilitate its interaction with the target DNA duplex. The research team married the machine learning and high-throughput screening platforms to design activity-enhanced SaCas9 protein by combining mutations in its PI and WED domains surrounding the DNA duplex bearing a (PAM). PAM is crucial for Cas9 to edit the target DNA and the aim was to reduce the PAM constraint for wider genome targeting whilst securing the protein structure by reinforcing the interaction with the PAM-containing DNA duplex via the WED domain.

In the screen and subsequent validations, the researchers identified new variants, including one named KKH-SaCas9-plus, with enhanced activity by up to 33% at specific genomic loci. The subsequent protein modelling analysis revealed the new interactions created between the WED and PI domains at multiple locations within the PAM-containing DNA duplex, attributing to KKH-SaCas9-plus’s enhanced efficiency.

Until recently, structure-guided design has dominated the field of Cas9 engineering. However, it only explores a small number of sites, amino-acid residues, and combinations. In this study, the research team was able to illustrate that screening with a larger scale and less experimental efforts, time and cost can be conducted using the machine learning-coupled multi-domain combinatorial mutagenesis screening approach, which led them to identify a new high-efficiency variant KKH-SaCas9-plus.

The Assistant Professor of the School of Biomedical Sciences, HKUMed stated that this approach will greatly accelerate the optimisation of Cas9 proteins, which could allow genome editing to be applied in treating genetic diseases more efficiently.

© 2022 OpenGov Asia – CIO Network Pte Ltd.