THE CHANG LAB

Research Areas

Therapeutic Cells

Human-associated microbial communities are closely connected with our health states and physiological functions. Through bioprospecting and omic analysis of the human microbiota, we aim to identify and elucidate biological mechanisms which regulate the homeostatic interactions between human host and its microbiota. Working with clinicians, immunologists and microbiologists from the NUS Synthetic Biology consortium, we reprogramed the human microbiota into functional probiotics with prophylactic and therapeutic properties against human infectious disease, immune and metabolic disorders. The designer probiotic can be engineered to autonomously modulate host metabolism through dietary inputs dictated through host’s diet or through direct sensing of host-microbiota biochemistry.

therapeuticcell

Synthetic Genomics

A key objective of synthetic genomics is to develop novel generic platforms for biotechnology and innovations to societal problems such as drug resistance, energy crisis and environment pollution. SynCTI is part of the international consortium, comprising of New York University, John Hopkins University, Tianjin University, Tsinghua University, University of Edinburgh, Imperial College London, MacQuarie University, Genscript and the Beijing Genomic Institute, to develop the world’s first synthetic eukaryotic cell genome. Using an array of bioinformatics and genome editing tools, we will design and build a modified version of baking yeast’s chromosome XV. The synthetic yeast is equipped with novel functionalities that enables the direct interrogation of evolutionary questions not otherwise approachable and will be the basis of major breakthroughs in contemporary clinical and industrial biotechnology.

syntheticyeastgenome

Engineered Cell Factories

Microbial hosts are versatile platforms to produce valuable organic molecules from inexpensive renewable raw materials. Here, we apply synthetic- and systems-biology principles and incorporate artificial metabolic pathways into microbes for the production of biochemical, fuels, nutraceuticals and pharmaceutical ingredients. To further enhanced productivity and yield of the engineered cell factories, we developed high throughput screening platforms that can be used in combination with synthetic DNA parts library and directed evolution techniques to screen for robust cell factories with strong industrial potential.

engineeredcellfactories

Cell-based and Cell-free Biosensors

Synthetic biology provides a rational framework for the design and reprogramming of genetic regulatory circuits into biosensors. Biosensors developed in this respect can be used for the sensing of infectious pathogens, human diseases, environmental pollutants, heavy metals, or even metabolites from cell factories for directed evolution and high throughput screening applications. In complement with our high throughput screening facility setup, we are developing cell-based and cell-free biosensors for the aforementioned applications on various microbial and mammalian systems.

cellbasedcellfreebiosensors

Mammalian Synthetic Biology

Regulatory genetic circuits can be interfaced with endogenous signaling mechanism of mammalian cells to regulate cellular functions. This can be achieved by introducing prosthetic networks into mammalian cells to sense and respond to changes in cellular metabolites, hormones and cell-type specific transcription factors. Mammalian cells can also be functionalized with optogenetic control elements so that cell fate can be accurately regulated using specific light frequency. In SynCTI, we are applying synthetic gene regulation into the design and control of CHO cells for the discovery and scaled-up production of drug targets and novel therapeutic compounds.

mamaliancell

Funding Agencies