Infectious Disease Research

Susceptibility to infectious diseases may involve genetic variations that are discernible through genomic interrogation. However, there is a second dimension of complexity—a "second genome" originating from the pathogen. Studying pathogens in infectious diseases presents additional challenges, because the medically important pathogenic species are far more diverse than the human hosts they infect. This makes infectious disease a natural fit in the Genome Architecture and Design domain at GIS, where the theme of “Any Genome, Any Analysis, Any Scale” is of paramount importance for studying pathogen behaviour.

Functional genomic approaches also have great utility in infectious disease research. Many of the high-throughput technologies currently in use (even in human systems) today were originally pioneered in or originated from microbial systems, due to inherent advantages in these systems for genetic manipulation and technology. These technologies include the use of largescale mutagenesis and screening (including with transposons), comparative genomics and comparative functional genomics, and CRISPR-based technologies. More recently, single-cell genomics provides a new horizon for simultaneously exploring host and pathogen gene expression, overlaying a dynamic interaction layer onto the genetic susceptibility mentioned above.

Importance of Infectious Disease Research at GIS

Singapore has experienced several significant infectious disease outbreaks since the founding of GIS, including SARS, H1N1, Group B Streptococcus, Zika, and, most recently, COVID-19. Infectious disease research is therefore a pillar of Singapore’s health and biomedical sciences strategy. GIS has played a key role in providing genomic expertise in combating all of these outbreaks. Importantly, genomics is now the gold standard technique for outbreak detection and tracking. Further research into infectious disease genomics is important for preparing Singapore, and the world, for the next inevitable outbreak. The universal applicability across all organisms and disciplines means that genomics also expands beyond human health into food safety and environmental monitoring, especially water. Recent highlights of GIS’ infectious disease research include collaborative studies to investigate local hospital outbreaks, the Zika virus outbreak, and the yusheng-associated Group B Streptococcus outbreak.

Pressing Concerns in Infectious Diseases

Two pressing concerns related to infectious diseases are pandemic risk and antibiotic resistance. The former has been acutely demonstrated by the COVID-19 pandemic, which has rocked the entire world within a matter of months. Earlier, faster, and more widespread genomics capabilities are among the clear key upgrades that the global community requires to mitigate the threat of current and future pandemics and outbreaks. The current outbreak detection and analysis research efforts at GIS are well positioned to dovetail with continued decreases in genome sequencing costs. A key effort will be increased automation and scale that would allow other government agencies within Singapore (such as MOH, SFA, and NParks) to leverage these capabilities.

The threat of antibiotic resistance is a broad cross-industry and all-of-society issue. Key economic, social, and policy tools will be required to reach a solution. Genomics in infectious disease research may contribute to the traditional path of new drug discovery or provide alternative new strategies to turn the tide against antibiotic resistance. This broad problem requires both approaches, and no single institution will be able to pursue all of the efforts required. GIS’ infectious disease research portfolio maintains capabilities that contribute to the overall national and global effort, addressing both needs for new anti-infective therapeutics and alternative strategies to reduce antibiotic resistance rates using evolutionary and synthetic biology technologies.

Dr Swaine Chen