Challenges, experiences, and potential support for Asian moms in the workforce

Researchers Identify Gene Mutation in Lung Cancer Unique to Asian Population

Genetics of Asian lung cancer cohort reveal new biological insights on the tumorigenesis of non-small cell lung cancer (Source: Lee Yi Fei/A*STAR’s Genome Institute of Singapore. Created with BioRender.com)

22 July 2024 - Scientists from A*STAR’s Genome Institute of Singapore (GIS) and Bioinformatics Institute (BII), Cancer Science Institute of Singapore and National Cancer Centre Singapore have identified a gene, known as PARP4, that is frequently mutated in Asians but was not previously linked to lung cancer. 

Their discovery, published in Genome Medicine on 22 July 2024, was the outcome of large-scale sequencing efforts to better understand Asian disease biology. This study is part of the Open-Fund Large Collaborative Grant (OF-LCG) programme funded by the National Medical Research Council (NMRC) to tackle Asian lung cancer.

Lung cancer is among the most frequently occurring cancers and a leading cause of cancer mortality worldwide. Among lung cancer cases, lung adenocarcinoma (LUAD) is the most prevalent histologic subtype, accounting for 38.5% of all cases. The OF-LCG program currently curates the largest Asian dataset for this subtype of lung cancer.

Leveraging on the team’s expertise on whole-exome sequencing of the largest Asian LUAD patient data, genes that had not been previously implicated in driving lung cancer were discovered. By using different lung cancer models, the researchers discovered that PARP4 acts as a tumour suppressor, where tumours grew faster in the absence of PARP4. Through a combination of experimental and computational modelling approaches, a recurring mutation in PARP4 was found to destabilise the protein, disrupting its interactions with other protein partners. A key protein partner is the splicing protein – hnRNPM – which is associated with PARP4 to slow tumour formation. hnRNPM controls the process of splicing, which is a crucial step in precisely translating genetic instructions encoded in the human DNA into protein production. When either PARP4 or hnRNPM was removed from the cancer cells, splicing was affected, in turn leading to errors in translation. Furthermore, as PARP4 expression levels were inversely correlated with patient overall survival, this may be exploited as a biomarker to track lung cancer.

Through this discovery, the researchers will now be able to explore ways to reactivate PARP4 function to slow down tumour growth and look for drug combinations that can specifically target and kill PARP4-mutant cancers.

Dr Tam Wai Leong, Deputy Executive Director at A*STAR’s GIS and Lead Principal Investigator for this study, said, “The discovery of PARP4 and other mutations in lung cancer highlights the importance of studying disease biology that may be unique to our Asian population, allowing researchers and clinicians to focus on targeted treatments and alternatives to slow tumour growth in cancer patients.”

Dr Darren Lim, Senior Consultant, Division of Medical Oncology at National Cancer Centre Singapore, said, “This paper illustrates the outcome of investing in a well curated repository of cancer data and models for common cancers in Singapore.  These data and models can be leveraged to bring about new discoveries such as this, that while early, hold the promise of new ways of treating non-smoker lung cancer prevalent in Asians.”

Towards lifelong vitality

Charting activity in genetic cityscapes

The ‘blood microbiome’ debunked

From weak start to top scientist: Genomics researcher pushes vaccine frontiers

Unfolding RNA origami reveals cell secrets

Dr Tam Wai Leong shares his opinion in Cancer Hallmarks: Piecing the Puzzle Together

GIS's spin-off Auristone secures US$4m in seed funding

SINGLE-CELL INSIGHTS TOWARDS PRECISION CANCER CARE

GIS RESEARCHERS DEVELOP FISHNCHIPS TO VISUALIZE DIFFERENT CELL TYPES WITHIN A DENSELY PACKED TISSUE

15 March 2024 - In biology, cells are the fundamental units of life, playing vital specialized roles like neurons transmitting signals or immune cells fighting disease. Traditionally, the goal of spatial transcriptomics has been to identify individual cell types using individual marker genes within a tissue sample. But this can be as difficult as spotting a particular person from a distance in a crowd. Just as individual features may be indistinguishable from afar, markers for certain cell types can also be too faint or blurry.

A team of researchers from A*STAR’s Genome Institute of Singapore (GIS) recently published a paper in Nature Communications to address this challenge. Principal Investigator and Group Leader at GIS’ Laboratory of Imagenomics, Dr Kok Hao Chen, Dr Nigel Chou and their team are early developers of spatial transcriptomics technologies in their research and wanted to derive an assay that would be more cost-effective and scalable. By using sets of genes, they developed FISHnCHIPs (Fluorescence In Situ Hybridization of Cellular HeterogeneIty and gene expression Programs), which maintains or even improves the robustness and sensitivity of the assay. The FISHnCHIPS method elegantly solves this challenge by looking at combinations of co-expressed markers instead of individual markers. The key insight is that genes involved in the same biological processes or pathways are co-localized within the same cells. Rather than relying on individual marker genes, FISHnCHIPs targets the entire gene programs. This allows it to rely on the multidimensional molecular "fingerprints" to robustly detect and distinguish different cell types. This enhanced sensitivity allows rapid, sensitive, and robust whole-tissue profiling under low magnification, and applicable for analyses of clinical tissue samples with low RNA quality. Remarkably, FISHnCHIPs also works robustly in frozen human samples, opening new avenues for discovering the spatial origin of rare cell types in disease. For more information, read the full article at: Protocols & Methods

INSPIRING THE NEXT GENERATION OF SCIENTISTS!

6 March 2024 - Genome Institute of Singapore (GIS) together with A*STAR Graduate Academy, was at the annual Singapore Science and Engineering Fair held at the Singapore Science Centre on 6 March. Dr Claire Bellis and Dr Roy Ang shared about the scientific work they do on DNA extraction and plant biodiversity at GIS, inspiring many young students about the research work in genomics and a possible career in scientific research in future.

BRIGHT SPARKS FROM GIS

GENE EDITING CUTS TO THE CHASE

GIS RESEARCHERS COLLABORATE WITH CLINICIANS TO REVIEW ROLE OF SKIN MICROBIOME IN ECZEMA

3 February 2024 - Atopic dermatitis (eczema) is a common recurring skin condition affecting 25% of children and has a substantial impact on their quality of life due to highly visible flares, itching and a loss of self-esteem. Eczema is often subsequently accompanied by other chronic conditions such as food allergies and auto-immune diseases. Thus, there is great clinical interest in early prevention of eczema in children. However, eczema is a clinically heterogenous disease and flares can be triggered or exacerbated by multiple factors such as patient genetics, irritants from the environment or even the bacteria that reside on our skin.

Dr Niranjan Nagarajan, Principal Investigator at A*STAR’s Genome Institute of Singapore (GIS) and Dr Minghao Chia, GIS fellow, collaborated with clinicians from the National University Health System (NUHS) of Singapore and other domain experts from A*STAR Skin Research Labs (A* SRL) and National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH) in the United States to author a review about the complex interplay between human genetics, the immune system and the skin microbiome in the aetiology of AD and food allergies.

In this review “The skin microbiome in pediatric atopic dermatitis and food allergy” published in Allergy, the team summarized the current scientific understanding of the role of the skin microbiome in eczema. Topics covered include the possible molecular mechanisms by which microbes worsen or protect against eczema and food allergies, how early life (< 1 year) skin microbial signatures may be predictive of future disease, how household transmission of microbes may contribute to eczema recurrence, and how immunotherapies can shape the skin microbiome. Importantly, many of these findings were made possible due to advances in genomic technologies. The authors also identified several promising clinical trials harnessing the skin microbiome for targeted treatment of eczema and food allergies such as the topical application of protective microbes or their products.

Nagarajan and Chia believe that state-of-the-art genomic technologies can help with dissecting the factors that contribute to eczema. “Technologies like Nanopore long read sequencing, metagenomics (DNA seq) and metatranscriptomics (RNA seq) can identify eczema-associated human and microbial pathways or products which can vary across patients. This is crucial for better patient stratification and targeted treatment,” said the researchers from GIS.

The authors also highlighted gaps in existing literature that should be prioritized in future work. First, researchers need to determine whether changes in the skin microbiome can influence eczema severity or are just signs of disease or treatment. Second, the integration of genomics, microbial culture-based experiments and host measurements are needed for a mechanistic understanding of the role these factors play in disease. Third, time-course studies are required to pinpoint the best time for intervention for greatest clinical efficacy. Fourth, more clinical trials should be conducted to assess how host and extrinsic factors modify the effectiveness of microbe-based therapies for managing eczema and food allergies.

Nature Communications Editor Shares Insights on scientific publishing

25 January 2024 - Dr George Inglis, Senior Editor at Communications Biology, delivered an insightful seminar on the editorial process of scientific publishing in Nature Portfolio. He kicked off the session with a sharing of his personal journey to becoming an editor at Communications Biology, an open access journal from Nature Portfolio that publishes high-quality research, reviews, and commentary in all aspects of biological sciences.

He also expounded on the editorial process outlining each stage, from the initial submission of the paper by the researcher or scientist, to the meticulous editorial and peer review processes of the paper before the editors decide if the papers are to be accepted or rejected. Dr Inglis cited two main reasons for rejecting a paper: the topic being out of scope, or similar findings having been already published by other journals. In rare cases, the conclusions are not backed by data. He also reassured researchers that they will be guided by the handling editor throughout the entire editorial process.

More importantly, Dr Inglis highlighted the importance of including a concise cover letter for the editor when submitting their papers as this could be an opportunity to highlight the biggest takeaways of their study and distinguish it from other studies that may be similar.

The seminar provided invaluable insights into the editorial landscape for our researchers, equipping them with the knowledge and clarity on the scientific publishing process.

GIS Welcomes GYSS Participants

GIS RESEARCHERS SELECTED FOR PRESTIGIOUS NRF INVESTIGATORSHIP AND FELLOWSHIP

CAN TERRESTRIAL CROPS GROW ON MARS?

25 November 2023 - In an experiment by A*STAR’s Genome Institute of Singapore (GIS) and SingHealth Duke-NUS Institute of Biodiversity Medicine (BD-MED), researchers are experimenting with growing plants in regular soil against Mars simulant soil. Their exhibit is part of the “Mars: The Red Mirror" exhibition held at the ArtScience Museum. At the scientific symposium on 25 November, Dr Roy Ang (GIS’ Scientist from Laboratory of Biodiversity Genomics) shared the stepping-stone research that scientists are undertaking to advance understanding of what it takes to grow crops on Mars.

This plant experiment is an initiative by Space Faculty and is jointly prepared by scientists at A*STAR’s Genome Institute of Singapore (GIS) and the SingHealth Duke-NUS Institute of Biodiversity Medicine (BD-MED).

A key factor to sustaining human life on Mars is the ability to grow and produce food on the Red Planet. Data from NASA’s Curiosity rover has provided us with an understanding of Martian soil and has enabled scientific organisations to produce Mars simulant soil – Mars Global Simulant (MGS-1), a mineralogical standard analog. MGS-1 is made by sourcing a spectrum of terrestrial minerals and mixing them together in specific proportions to generally replicate the Martian surface.

In this exhibit, the model plant Arabidopsis thaliana and common vegetable crop ‘Kailan’ Brassica sp. are grown in two different soils: Earth soil, and Mars simulant soil – supplemented with fertilizer solution. Fertilizer supplementation in Martian simulants is necessary for plant growth due to a lack of key plant nutrients. Experiments such as these not only help scientists understand how life on Mars could work, but may also have implications for life on Earth as our environment changes.

>div>

2ND PAN-ASIA SYMPOSIUM ON GENETICS OF BRAIN DISORDERS

3 - 5 November 2022 - The 2nd Pan-Asia Symposium on Genetics of Brain Disorders organised by the Genome Institute of Singapore, Institute of Mental Health, NTU’s Lee Kong Chian School of Medicine, NUS’s Yong Loo Lin School of Medicine and the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard. Photo credits to LKCMedicine, NTU

From 3rd to 5th November 2022, the 2nd Pan-Asia Symposium on Genetics of Brain Disorders brought international experts in neuropsychiatric disorders together to share their latest findings on the genetics of brain disorders and to pave the way for effective therapeutics.

Genetic studies have uncovered changes in particular genes that holds promise to better understanding and treatment of neuropsychiatric disorders. However, the Asian population is under-represented in these studies. Efforts have been made to bridge this gap through the Psychiatric Genomics Consortium (PGC) Schizophrenia Asia working group and the Stanley Global Neuropsychiatric Genetics Initiative. This is a gap that international experts at the symposium have focused on to translate genomic findings into better treatments for the Asian population. 

Leading scientists and clinicians from around the world including Prof Liu Jian Jun, Deputy Executive Director and Distinguished Institute Fellow at the Genome Institute of Singapore, discussed significant clinical, genetic and translational aspects of neuropsychiatric disorders during this two-and-a-half-day hybrid conference.

Organised with the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, a global leader in neuropsychiatric research, this symposium brought together leading geneticists, neuroscientists and clinicians from Stanley Center and Singapore to foster future collaboration in neuropsychiatric research in Singapore. The conference hosted by NTU’s Lee Kong Chian School of Medicine was held in Asia to facilitate Asian collaborations in neuropsychiatric research in the region. It was organised by the Genome Institute of Singapore, Institute of Mental Health, NTU’s Lee Kong Chian School of Medicine, NUS’s Yong Loo Lin School of Medicine and the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard.

(Photo credits to LKCMedicine, NTU)