Short microbial generation times, large population sizes, and high mutation rates mean that microbes have the potential to accumulate genetic modifications so rapidly that these changes could impact simultaneous changes in species composition (presence and abundance of species and strains caused by environmental constraints) and in their interactions with each other and the environment. Microbial communities can rapidly respond to environmental change (e.g. threat of extinction), but the proportion of this response that can be attributed to evolutionary processes, rather than species composition or gene expression shifts, remains unresolved. Population metagenomics approaches are needed to address this question.
Metagenomes constitute pooled genomes of populations which in extreme cases may consist of thousands of species, are largely sparse, and prone to erroneous data. Conducting an accurate population genetic analysis with them requires adjustments to the existing statistics and development of novel methods. Therefore, I first focused on developing theory, then on extending the developed and existing methods to metagenomes, and then used these novel tools to analyse rhizobiome community data to understand eco-evolutionary processes and plant-soil interactions.
This 4th Annual Symposium ― Mycobacteria 2026: Translating Biology into Cures will bring together leading scientists, clinicians, pharma and innovators from around the globe to share the latest breakthroughs in Tuberculosis (TB) and non-tuberculous mycobacteria (NTM) research and drug discovery. The goal of this event is to discuss novel concepts and to provide a platform for vibrant and open discussions between industry, clinicians and senior scientists, postdoctoral fellows and students from academia.
Registration is free but compulsory and from the submitted abstracts short oral presentations will be selected.
Age-related macular degeneration (AMD) is linked to retinal pigment epithelium (RPE) dysfunction, where cellular senescence disrupts proteostasis and endoplasmic reticulum (ER) homeostasis. Here, a tert-butyl hydroperoxide (TBHP)-induced senescence model in human RPE1 cells was established to investigate how senescence alters IRE1-mediated unfolded protein response (UPR) signaling. Senescent cells exhibited a markedly weakened UPR under both proteotoxic and lipid bilayer stress. Although XBP1 mRNA splicing was induced, XBP1s protein was completely absent, indicating impaired translation. Senescence also intrinsically activated the regulated IRE1-dependent decay (RIDD) pathway, supported by basal degradation of the canonical RIDD substrate BLOC1S1 and RNA-seq-based identification of additional putative RIDD targets for future validation. Structurally, senescent cells showed severe ER fragmentation, which was aggravated by IRE1 loss but rescued by XBP1s overexpression. These findings demonstrate that senescence impairs IRE1 signaling, weakens ER stress resilience, and may contribute to AMD pathogenesis, highlighting IRE1-XBP1s restoration as a potential therapeutic strategy.
The function of many plant genes cannot be elucidated from their coding sequences, as many of them are lineage-specific, orphan genes, or possess multiple functions. In recent years, the genomes of plant species have been continually sequenced, and public plant gene expression data (in the form of public RNA-seq accessions) are rapidly accumulating owing to the advancement and increasing affordability of sequencing technologies. Gene Co-expression Networks (GCNs) can be used to take advantage of this unprecedented wealth of public transcriptomic data available for the Plant kingdom to supercharge the prediction of gene functions. However, there exist methodological hurdles that impede the utilisation of GCNs for this purpose. My research focuses on addressing these gaps.
Malaria and cancer continue to pose major global health challenges, and the emergence of drug resistance limits the long-term effectiveness of current therapies. The work of my thesis concerns the use of chemical synthesis and enzymatic protein modification approaches, respectively, for the design and engineering of anti-malaria and anti-cancer drug molecules that have the potential to overcome the resistance problem of current therapies.
The chemical approach involves systematic structure–activity relationship study on a previously discovered antimalarial lead compound. The lead compound possesses structural features indicative of DNA binding ability. Qualitative and quantitative mechanistic studies were performed to assess DNA recognition and binding as one potential mode of action (MOA) for its antimalarial activity. Results from this study suggest DNA as an underexplored target space for discovering antimalarial molecules with MOA beyond classical protein-targeted mechanisms and less likelihood to develop drug resistance.
The enzymatic protein modification approach involves the use of peptidyl asparaginyl ligases (PALs) for site-specific antibody functionalization, specifically for the preparation of antibody-drug conjugates (ADCs). Orthogonal protein modification strategies were established by combining chemoselective and enzymatic PAL-mediated conjugation strategies, allowing precise and independent installation of two different cytotoxic payloads at distinct sites of the antibody molecule while preserving antibody binding activity and payload function. In addition, PAL-mediated ligation was expanded to thioester substrates, allowing ligation at non-Asn/Asp junctions and enabling applications such as D-peptide cyclization and antibody dual labelling.
In conclusion, these studies integrate medicinal chemistry and enzymatic approaches to generate antimalarial and anticancer molecules with unique mechanisms of action and multifunctional architectures for addressing drug resistance.
Cancer is a complex disease characterized by the uncontrolled proliferation of abnormal cells and remains a leading cause of mortality worldwide. Immunotherapy has emerged as an effective strategy to combat cancer and is broadly classified into active and passive approaches. Active immunotherapy aims to stimulate or restore the patient’s immune system to recognize and eliminate tumour cells, whereas passive immunotherapy involves the administration of exogenously prepared immune effectors, such as antibodies or immune cells, independent of endogenous immune activation. Although monoclonal antibodies are widely used in passive immunotherapy, their large size and long serum half-life limit tissue penetration, restricts access to certain epitopes. To overcome these limitations, nanobodies have been developed. Their small size (~15 kDa) and extended, flexible CDR3 loop confer high affinity and enable access to previously inaccessible epitopes. Furthermore, conjugation of nanobodies with diverse payloads using the VyPAL2–hQC cascade system expands their applications as drug conjugates, imaging probes, and PET tracers.
Plants have evolved two receptor systems to detect microbial threats and initiate successive defenses. Cell-surface pattern-recognition receptors (PRRs) perceive conserved pathogen-associated molecular patterns (PAMPs) and trigger pattern-triggered immunity (PTI). Intracellular nucleotide-binding leucine-rich repeat (NLR) proteins monitor pathogen-delivered effectors and activate effector-triggered immunity (ETI). Phytopathogenic bacteria, fungi, oomycetes, and insects deploy diverse effectors to undermine host defenses. Many effctors have enzymatic domains that modify host targets for function perturbation. However, prior work has largely overlooked intrinsically disordered regions (IDRs) within effectors, which may confer unique activities without folded domains. Here, we focused on XopR, a highly disordered effector from Xanthomonas campestris pv. campestris. Using an effector-less pathogen, we developed a new delivery method for XopR. Leveraging this tool, in vitro reconstitution, live-cell imaging, and biochemical assays, we found that XopR’s multivalent binding induced clusters of PRR complex components at the plasma membrane. Such clustering impaired endocytic turnover and sustained PAMP signaling. We also observed that XopR interacted with NADPH oxidase and blocked the conformational activation required for reactive oxygen species production. To identify XopR partners systematically, we performed a TurboID proximity-labeling screen and uncovered RIN4, a key guardee for the NLRs RPM1 and RPS2. We demonstrated that XopR remodeled RIN4 biomolecular condensates, altering RIN4’s material properties and immune activation. Finally, we employed hydrogen–deuterium exchange/mass spectrometry to map molecular dynamics within XopR–RIN4 coacervates. We identified several critical regions that contained previously known RIN4 regulatory sites, enabling further validation. Overall, we showed that IDR-rich effectors subverted host immunity by driving multivalent clustering, perturbing protein conformations, and reshaping the material properties of host biomolecular assemblies.
Plants have evolved two receptor systems to detect microbial threats and initiate successive defenses. Cell-surface pattern-recognition receptors (PRRs) perceive conserved pathogen-associated molecular patterns (PAMPs) and trigger pattern-triggered immunity (PTI). Intracellular nucleotide-binding leucine-rich repeat (NLR) proteins monitor pathogen-delivered effectors and activate effector-triggered immunity (ETI). Phytopathogenic bacteria, fungi, oomycetes, and insects deploy diverse effectors to undermine host defenses. Many effctors have enzymatic domains that modify host targets for function perturbation. However, prior work has largely overlooked intrinsically disordered regions (IDRs) within effectors, which may confer unique activities without folded domains. Here, we focused on XopR, a highly disordered effector from Xanthomonas campestris pv. campestris. Using an effector-less pathogen, we developed a new delivery method for XopR. Leveraging this tool, in vitro reconstitution, live-cell imaging, and biochemical assays, we found that XopR’s multivalent binding induced clusters of PRR complex components at the plasma membrane. Such clustering impaired endocytic turnover and sustained PAMP signaling. We also observed that XopR interacted with NADPH oxidase and blocked the conformational activation required for reactive oxygen species production. To identify XopR partners systematically, we performed a TurboID proximity-labeling screen and uncovered RIN4, a key guardee for the NLRs RPM1 and RPS2. We demonstrated that XopR remodeled RIN4 biomolecular condensates, altering RIN4’s material properties and immune activation. Finally, we employed hydrogen–deuterium exchange/mass spectrometry to map molecular dynamics within XopR–RIN4 coacervates. We identified several critical regions that contained previously known RIN4 regulatory sites, enabling further validation. Overall, we showed that IDR-rich effectors subverted host immunity by driving multivalent clustering, perturbing protein conformations, and reshaping the material properties of host biomolecular assemblies.
The 6th meeting of the Singapore Malaria Network intends to foster new ideas and concepts by bringing together scientists working in multiple aspects of malaria.
Understanding genome regulation requires linking 3D chromatin organization with cellular responses to perturbations, yet current experimental approaches are limited by cost, sparsity, and noise. This work presents two data-efficient computational frameworks to address these challenges. Small-ChINNpredicts chromatin interactions from small-scale Hi-C libraries by combining DNA sequence features and genomic distance, enabling recovery of biologically meaningful interactions without deep sequencing. The method generalizes across cell types, assays, and clinical samples, and performs robustly even in sparse single-cell datasets. Complementarily, VirtuGraph-Cell models single-cell perturbation responses using graph transformers, capturing gene regulatory structure and predicting responses to unseen perturbations. Together, these approaches demonstrate that genome regulation can be learned from limited data when appropriate structural priors are incorporated, providing a foundation for scalable, predictive modeling of genome function in both research and clinical settings.
Acinetobacter baumannii (Ab) is a pathogen of concern for its high resistance against antibiotics resulting in a high death toll, against which a novel and specific treatment is required. Ab relies on the F1FO-ATP synthase for ATP formation, maintaining ATP/ADP as well as pmf homeostasis. This thesis demonstrates that the AbF-ATP synthase regulates ATP hydrolysis via its ε subunit, with the εI134–Q139 as the major inhibitory element. Cryo-EM studies reveal multiple conformational changes in the ATPase-active enzyme, as well as in respond to ATP synthesis conditions. Functional analysis into the proton translocating FO-domain of the enzyme highlights the front entry in subunit a as the main proton uptake pathway, key residues involved in proton translocation and the proton exit channel, as well as the ratchet function of the unique a-subunit helix. Together, these structural and functional insights shed light into novel AbF-ATP synthase targets for inhibitor design.
The 3rd Annual Symposium: Innovations in anti-mycobacterial Drug Discovery will include presentations from speakers from around the world who have made significant advances in TB- and NTM research and –drug discovery. The goal of this event is to present novel concepts and to provide a platform for vibrant and open discussions between industry, senior scientists, postdoctoral fellows and students from academia.
The symposium is organized by members of TELMabNet (Targeting energy of life for the development of drug combinations to eradicate antibiotic-tolerant Mycobacterium abscessus, a clinical nightmare, Network), an excellence cluster funded by the Singapore National Research Foundation.
Understanding the mechanical properties of plants and their response to environmental factors is essential for developing innovative and sustainable solutions to address the challenges facing agriculture and forestry. 'Plant Biomechanics for Sustainable Agriculture and Forestry’, co-organized by Nanyang Technological University-Singapore, and Zhejiang Agriculture & Forestry University-China, will delve into the critical intersection of plant biomechanics and its impact on sustainable agriculture and forestry. The conference scheduled to take place from May 19-22, 2024 in Singapore at NTU. The event will feature a distinguished lineup of Plenary Speakers and host presentations from invited speakers representing prestigious institutions, ensuring a comprehensive and diverse range of perspectives.
This conference aims to foster collaboration, knowledge exchange, and networking opportunities among researchers, scientists, and industry professionals working in the field of plant biomechanics. It will provide a platform for the dissemination of the latest research findings, innovative methodologies, and sustainable practices that contribute to the advancement of agriculture and forestry.
We invite all participants to engage in this enriching and rewarding experience, with the goal of fostering meaningful discussions and collaborations that will contribute to the sustainable future of agriculture and forestry. We look forward to welcoming you to this important gathering and to the valuable insights and contributions you will bring to the conference.
The workshop is funded by the Zhejiang Agriculture & Forestry University (ZAFU), China and Nanyang Technological University, School of Biological Sciences (SBS).
Join us in the celebration of our achievements through this research symposium where we invite our alumni, graduate students and postdocs to share their discoveries.
Speaker:
Professor Ernst H.K. Stelzer Bunchmann Institue for Molecular Life Sciences, Goethe Universität Frankfurt am Main
Hosted By:
Prof. Peter Török, A/P Li Hoi Yeung
