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1. Biomimetics

We have initiated a close collaboration with the Biological & Biomimetic Material Laboratory at NTU to characterize and engineer high performance materials from marine organisms. We use an inter-disciplinary approach, integrating genomics, proteomics and materials science. By doing so, we can rapidly identify the protein sequences of a wide range of biomaterials for structure-function analysis and biomimetic engineering. Current biomaterials under investigation include the Squid Sucker Ring Teeth, Squid Beak, Marine Sea Snail Egg Capsule and Mussel adhesives.

2. Biosynthetic Pathways

Resources for novel chemical scaffold discovery, i.e polymers for materials or privileged scaffolds for drug development purposes, have slowly stagnated over the years. With the advent of next generation sequencing, the cost of sequencing has reduced significantly over the years, resulting in thousands of sequenced genomes already deposited in the publicly accessible NIH Genbank. This trend, along with the acceleration of synthetic biology and metabolic engineering technologies, have led us to re-visit natural product discovery. Using bioinformatics, protein engineering and metabolic engineering, we envision a rapid, high throughput discovery platform for novel chemical scaffolds. This platform will also enable us to construct de novo metabolic pathways towards known high value chemicals.

3. Genetic Switches

We are interested in the development of genetic switches for the control of gene expression in bacterial and mammalian systems. We aim to apply these switches to the control of cellular differentiation.

4. Human Disease Modelling

Recent advances in stem cell research, especially the development of induced pluripotent stem cell (iPSC) technology, provide new opportunities which may overcome many of the challenges and shortcomings associated with disease modeling and drug screening. Many neurological disease phenotypes can be measured on high-content imaging platforms through changes in cellular morphology. In addition, changes in biochemical activity and gene expression could also be used as assay readouts for drug screens.

Currently, most iPSCs are generated using reprogramming factors transduced by integrating viral vectors such as lentivirus or retrovirus, which often cause mutations at the integration sites or other genetic aberrations such as copy number variations or abnormal karyotypes. Genetic alteration by random viral integration may affect the differentiation of iPSCs as well as their phenotypes. Recently, strategies have been developed for the generation of transgene-free iPSCs to minimize or eliminate genetic variations.

In our lab, we are using mRNA and episomal reprogramming to generate iPSCs from fetal tissue and cord blood. In turn, we hope to convert these iPSCs into other cells types that could be used for drug assays in neurological diseases.

 

5. 3D Cell Culture

Multicellular spheroids are useful 3D cell culture models that closely resemble the complex microenvironment in tissues in vivo. In MEL, we have developed a simple and versatile methodology for generation of magnetic multicellular spheroids. They can be manipulated using magnetic field gradients. This would be convenient for spheroid patterning or separation. We are interested in using magnetic spheroids in applications such as tissue engineering, tumour studies and drug screening. We have established spheroid-based assays in prolonged therapeutics studies which are potentially amenable to high throughput screening equipment.With our platform, we hope to bridge the gap between in vitro and in vivo systems and provide beneficial insights which could otherwise be missed in 2D monolayer assay.


6. Molecular Probes Development

We are developing molecular probes for various sensing applications involving nucleic acid and proteins.
 

Technologies Employed

1. Next-generation Sequencing

2. Protein Engineering

3. Chemical Synthesis

4. Human ES/IPS cell programming

5. Genome Editing