Research in cellular and molecular biology covers various aspects of molecular biology, developmental biology, functional genomics, metabolomics, stem cells, as well as plant molecular biology.
Molecular recognition is the basis for all cellular events – from a simple bimolecular enzymatic reaction to the cascades of multimeric protein complexes in cell signaling. Fundamental to the structure and function of a protein is its ‘domain’, which refers to a discrete, minimal mods. Several DBS research groups are engaged in investigations related to cell signaling to identify novel signaling proteins and protein domains that control cell growth and tissue/organ development in normal and disease states. The general research interests include cell signaling, domain-discovery, protein-protein interaction, structural biology, developmental biology, computational biology and mechanobiology.
Fish systems are models for understanding several types of interactions with the environment. Several of these have unique features such as abilities to withstand adverse conditions, including tolerance to high levels of ammonia in the body. For example, induction of aestivation in African lungfishes on land can facilitate studies on metabolic rate reduction, regulation of ammonia production and suppression of activities in the central nervous system. Hence, understanding the underlying mechanisms of aestivation will provide a better grasp of the unique stress tolerance mechanisms. Just as fish are screened for anti-cancer drugs and plants filter toxins from water, fish are now used in environmental toxicology. DSB groups have used the same transgenic technology to develop several bio-monitoring transgenic fish for detecting different pollutants in water.
Host-pathogen interactions DBS researchers study virus, bacterial, and fungal interactions with host cells as models for immunity, infectious disease, and technology development. In studies of innate immunity and pathogen surveillance, one group has discovered new and important functions of several immune-responsive molecules which are evolutionarily conserved for 500 million years.
Several DBS faculty study the molecular biology and structure of plant, animal and human viruses including Orchid and Hibiscus viruses, fish viruses, and the human virus, Dengue. These infectious agents perturb the physiology of their host. One group works towards understanding the role of metabolites in the functional ecology of plant and environmental bacterial systems. Their work involves understanding:
- Structure and dynamics of metabolic networks in response to genetic or environmental perturbations;
- Signaling system of cyclic diguanylate that coordinately regulates diverse pathways such as motility, biofilm, and secretion systems.
Agrobacterium tumefaciens can act as a bio-syringe to deliver T-DNA into different eukaryotic cells, including those of plants, yeast, fungi and humans. T-DNA is delivered in the form of a nucleoprotein complex. Agrobacterium to eukaryote gene transfer may be used as an excellent model system to study the fundamental process of nucleoprotein trafficking, which might be relevant to some of the issues in human gene therapy and HIV viral infection. Based on this knowledge, DBS researchers are currently designing and developing novel Agrobacterium-based DNA delivery systems for gene therapy and protein delivery systems for mammals, which may become desirable therapeutic systems of the future. Protozoan parasites remain good cell biology models. DBS researchers have uncovered how the characteristic beat of the Trypanosome parasite flagella is modified by its attachment to a crystalline rod in the cytoplasm. New investigations on organelle biogenesis and autophagy shed light on these basic mechanisms in animal cells.
Currently, several groups in our department are focusing on stem cell technology in fish and plant models with the goal to understand the molecular mechanisms involved in the maintenance of pluripotency and self-renewal capability of embryonic stem (ES) cells and organogenesis using several vertebrate models. An excellent model for vertebrate development is the fish medaka (Oryzias latipes). DBS research is home to the first fish ES cells, world-first male germ stem cells and haploid ES cells. Main technology breakthroughs include the generation of first test-tube sperm and a semicloned fish called ‘Holly’. Research into haploid ES cells and fish viruses are used in to the development of virus-resistant seed stock for sustainable and cost-effective aquaculture. Current studies are underway to identify and disrupt host factors that are used by viruses for infection via genome-wide insertional mutagenesis. Plant and human stem cells are being studied to understand the molecular mechanisms of stem cell maintenance, lineage specification and organogenesis during vertebrate development and plant root development. Stem cells are the basis for several efforts into stem cell technologies. One goal is the development of efficient strategies for the directed differentiation of human ES cells and direct conversion of somatic cells like fibroblasts into VMH neurons. Other studies investigate stem cell vehicles derived from iPS cells to deliver anticancer proteins to metastatic tumors through their tumor-homing property.
Several research groups study fundamental mechanisms controlling flowering and root formation in Arabidopsis and rice model systems. On the one hand, plant hormones, cytokinin and gibberellin signal plant development and senescence. Mechanisms of the control of flowering time, floral meristem specification, floral organ patterning and hormone signaling in reproductive development involving gene regulatory networks and chromatin-mediated or epigenetic mechanisms are a particular focus of research. The timing of the developmental transition from vegetative to reproductive phase (flowering) is controlled at the molecular level. Particular genes involved in regulation of vegetative shoot development are being identified by functional analysis of cDNAs. These studies into the mechanisms of development, flowering and senescence are fundamental for genetic improvement of crops such as rice and orchids, plants for fodder and feedstock for biofuels. DBS plant biologists and geneticists work with industry in their oil palm molecular breeding and functional genomics program to improve the yield of oil palm. The department has recently enlarged its plant growth facilities to cater to expand its basic and applied research of plants.
- Molecular and cellular mechanisms controlling the origin and development of cells, tissues and organs
- Regulatory processes that explain the emergence of higher order properties in a developmental system in a given environment
- Generate specific types of plant cells, tissues, organs or entire new plants
Basic understanding of plant physiology is important for managing plants interactions with the environment. Mangroves are important for the maintenance our Singapore’s shores and biodiversity. Research is underway to understand how the tropical mangrove plant, Avicennia, desalinates sea-water. The mechanism of salt uptake and secretion in the salt glands and the role of water channels will reveal how these plants to survive in a saline environment. Salt stress and drought are an increasing problem to crops in a changing climate. Research into the extraordinary abilities of plant roots to generate different types of new organs postembryonically may be applied to growing rice and other crops in unfavorable soil/environmental conditions. Similarly, tropical plant species may prove beneficial for phytoremediation of water, e.g. to remove contaminants like nitrates, bisphenol A and heavy metals. Thus fundamental studies on plants may lead to technologies that:
- Generate new crop varieties with or identify new agricultural chemicals that confer superior tolerance to multiple environmental stresses
- Desalinate and remove toxic chemicals from soil and water