Hongfang Lu and Andrew Wan
Cell plasticity refers to the ability of cells to be reprogrammed to other cell types, including stem cells. Our research efforts are focused on two fronts. First, we are trying to replace the more conventional cell reprogramming method, which typically involves genetic modification of cells, with transgene-free and xeno-free methods that dispense with the use of animal products. Through this, we hope to develop a safer source of cells for use in regenerative medicine. Our second research focus is on investigating the role of the cellular microenvironment in the reprogramming of cancer cells. We have shown that the extracellular matrix and 3D environment combine to influence the stemness of glioma cells, which is typically associated with the cells’ self-renewal and drug-resistance properties. This information would be useful in developing new cancer therapies.
Ziwei Song, Yu Yang and Hanry Yu
We have developed optical imaging modalities to quantify cellular and extracellular changes in tissues. The instruments and machine-learning based image-processing/feature analysis algorithms developed are used to automate and improve pathological examinations related to (i) liver fibrosis, (ii) cholestasis and (iii) non-alcoholic fatty liver diseases. This helps to shed light on the etiology of the diseases quantitatively. We have developed a high-throughput tissue imaging platform to quantify tissue/cell and matrix features of big blocks of tissue in mice or the entire biopsy sample at molecular and cellular resolutions for 3D characterization of disease progression. We have spun off an award-winning company, HistoIndex Pte Ltd, from this project, and licensed key technologies to another start-up company, InvitroCue Pte Ltd, to create an impact in the digital pathology and telemedicine landscape. The team is also investigating the fundamental process of liver regeneration by quantifying and modeling the mechanical and biochemical regulation of the cellular hypertrophy.
Farah Tasnim, Xiaozhong Huang and Hanry Yu
Cell-based assays for in vitro toxicity evaluation are attracting increasing attention from institutions and companies involved in the development of drugs and industrial chemicals. The major bottlenecks are the lack of stable human primary cells, and cell-culture models that recapitulate the in vivo physiological responses to the tested compounds. So far, only the sandwich culture of liver cells is accepted by the Federal Drug Administration (FDA) for routine hepatotoxicity testing of drugs. To improve the cell-based assays, we have developed (i) a scalable aligned substrate on optical media, (ii) two improved spheroid models for acute and chronic toxicity testing, respectively, (iii) a co-culture model for idiosyncratic toxicity, (iv) three perfusion-based models for improved sensitivity to detect metabolites, (v) a developmental toxin based on morphogenic migration of human stem cells, and (vi) stable and robust cell sources from human stem or progenitor cells. We are validating these established models for hepatotoxicity and teratogen testing of compounds, and improving the performance of these platforms for robustness, predictive fidelity, scalability and cost. We are also extending the applications of these models to sub-acute/chronic hepatotoxicity in order to better mimic “in vivo-like” conditions.
Zheng Liu (Justinian), Farah Tasnim and Hanry Yu
Complex tissues with multiple cell types will be engineered by controlling cell-cell and cell-matrix interactions through (i) engineering inter-cellular linkers for 3D printing, (ii) engineering cellular response to the chemical and mechanical signals by developing ultra-soft macroporous sponges that are robust, transparent, degradable and enhancing compact spheroid formation, and (iii) fabricating relevant 3D microfluidics, micro-patterns and ultra-thin porous membranes incorporating mechanical compaction and multiple cell types for organ-on-a-chip applications, such as a liver cancer chip to aid chemotherapy testing. This project establishes the fundamental principles, toolboxes and devices to precision-engineer micro-tissue constructs of different cell types and inter-cellular tissue space (such as sinusoid and bile canaliculi in liver) for repeated dose testing of compounds that require mid-term (> 2-4 weeks) or long-term (up to 6 weeks) culture of micro-tissue constructs.
Tze Chiun Lim, Chan Du, Yihua Loo, Wei Yang Seow, Benjamin Tai , Andrew Wan
Tissue engineering requires the use of a framework or scaffold for cells to attach and grow. In addition, scaffolds may contain biological molecules, which control the rate of cell growth and propensity of stem cells to differentiate into cells of specific tissues and organs. Most of the current processes for the production of tissue scaffolds require high temperatures and organic solvents, which may denature the proteins and other biological molecules to be incorporated. In this project, we are fabricating scaffolds by encapsulating cells and the relevant biological molecules into fibers that are formed at the interface between two oppositely charged polyelectrolytes. These fibers are then combined to form 3D patterned tissue constructs.
Jacqueline Chuah, Faezah Hussain and Daniele Zink
New alternative methods for toxicity prediction are required by the pharmaceutical, chemical, food and consumer care industries. Currently, there are no accepted alternative methods for the prediction of toxicities for human internal organs, such as the kidney and liver. We are developing robust screening platforms that predict toxicities to human internal organs with high sensitivity and accuracy (test balanced accuracy > 80%). Our methods include several novel technologies, such as the first in vitro assay that predicts nephrotoxicity in humans with high accuracy, the first stem cell-based predictive renal screening platforms, and the first predictive kidney-specific high-throughput platform. Our kidney-specific technologies have been awarded by the US Society of Toxicology (2015) and have won the Lush Prize (2016, Science category). The renal high-throughput platform is applied in collaboration with the US Environmental Protection Agency for the prediction of the human nephrotoxicity of ToxCast compounds. Our high-throughput technology is currently adapted for the prediction of other organ-specific toxicities. A liver-specific platform has been established, and a vasculature-specific platform is under development. Our methods can also be applied for the prediction of chemical- as well as nanomaterial-induced toxicities.
Yuan Yuan, Diane Lim and Yugen Zhang
Antimicrobial resistance (AMR) is one of the most critical challenges in our modern society. The overuse of antibiotics, including its use in non-therapeutic applications, such as agriculture and environmental disinfection, represents one of the main causes of antimicrobial resistance. IBN has developed a series of novel non-resistant, eco-friendly antimicrobial oligomers and polymers with broad-spectrum antimicrobial activities against bacteria, yeast and fungi. These have synergistic effect with small molecular antibiotics and prevent drug resistance development. Our novel antimicrobial materials will self-destruct after treatment, leaving no active residue that can lead to secondary environmental contamination. This is especially meaningful in the context of agricultural applications, topical use and environmental disinfection.
Xiukai Li, Jinquan Wang, Diane Lim, Siew Ping Teong, Wei Lun Toh and Yugen Zhang
IBN’s green synthesis research involves the use of sustainable resources for the environmentally friendly synthesis and investigation of green and benign chemical processes for the specialty chemicals industry. IBN researchers are developing green and safe chemicals for consumer care, healthcare and the food and nutrition industries. IBN is also creating functional materials for a broad range of applications including environmental, healthcare and medical applications.
Guangshun Yi, Siti Nurhanna Riduan, Yuan Yuan, Xiukai Li, Siew Ping Teong and Yugen Zhang
IBN has developed inorganic and non-toxic antimicrobial materials specifically for surface disinfection and consumer care applications. Our antimicrobial technologies kill microbes either by physically rupturing their cell membranes or by a radical killing mechanism, which prevents the microbes from developing drug resistance and mutating into superbugs. Our nanomaterials are inexpensive to produce, environmentally friendly and safe. They are effective against a wide range of microbes and would be a powerful weapon against superbugs.
Changliang Ren and Huaqiang Zeng
Marine oil spills can cause devastating and lasting damage to the environment and ecosystem, and are difficult to clean up using currently available oil-control techniques. We are developing cost-effective organogelators that can phase-selectively congeal oil from oily water, and allow easy separation of the gelled oil from water. It is made up of small organic molecules that can instantly self-assemble into nanofibers to form a 3D net that traps the oil molecules into clumps that can be skimmed off the water surface. This is a novel solution to clean up polluted water caused by oil spills.
Jie Shen, Feng Chen, Changliang Ren, Arundhati Roy and Huaqiang Zeng
Commercial use of water-transporting aquaporins has been explored for wastewater reclamation and re-use as well as seawater desalination. However, significant challenges associated with manipulating channel proteins in terms of complexity, stability, scalability and activity reconstitution still remain. An alternative strategy is to design small molecule-based synthetic water channels that can mimic aquaporins in functionality for various water purification applications. Towards this goal, we are developing synthetic water channel-based membranes to desalinate seawater with higher salt rejection rates at much lower pressures than the current seawater reverse osmosis technology. These novel biomimetic membranes could form the basis for the next generation of water purification technology with less energy consumption and better performance. In addition, the low production cost of the membranes makes it attractive for other potential applications, such as pharmaceutical separations, artificial skin and kidney.