The systematic understanding of complex biological systems altered in human diseases remains a major challenge to the future development of new approaches for disease diagnosis or therapy. The Integrative Chemical Biology theme at inStem seeks to develop an integrated platform to address this challenge, by combining the expertise and efforts of four different programmes.

Developing genetic & chemical tools to deconvolute biological pathways. Investigators at the Centre for Chemical Biology and Therapeutics (CCBT) will apply genome-wide screens using the CRISPR-Cas9 system to identify new targets that mediate rate-limiting steps in biological pathways, and develop selective chemical probes against such targets using structure-guided approaches that integrate biochemical and biophysical screens, structure determination using X-ray crystallography and NMR, computational and synthetic chemistry, and cell biological analyses.

In a complementary approach, investigators in the RNA Biosensor and aptamer programme are developing chemical tools and biosensors to study the regulation of fundamental processes such as protein synthesis driven by changes in signalling components and bioenergetics critical for cellular activity. The primary focus of this programme is to develop tools to manipulate and study changes in the modes of protein synthesis that regulate protein repertoire both in the normal and disease conditions using wide variety of structure, chemical and imaging tools

To enable the widespread application of these novel genetically-encoded and chemical probes for cellular imaging, investigators in the imaging programme will develop novel genetically-encoded and chemical tools to image and map cellular activity in real time. These sensors to measure protein activity, energetics and biochemical environment of the cell will enable widespread application, which include developing integrative bio-imaging methods and cellular diagnostics.

Delivery systems for genetic & chemical probes. To develop innovative systems for the delivery of novel genetically-encoded and chemical probes for applications ranging from human disease to agriculture, investigators in the Delivery programme will develop innovative chemical biology strategies to probe interactions between synthetic molecules/materials and biological systems. Through this approach new concepts and novel delivery systems will be generated.