Project Details
Projekt
An Open Source Next-Generation Maskless Array Synthesizer for Biological Photolithography and Applications in Ultra-Large-Scale Nucleic Acid Synthesis
Applicant
Dr. Mark Somoza
Subject Area
Biological and Biomimetic Chemistry
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 460736965
Biological photolithography uses optical approaches adapted from the integrated semiconductor industry combined with lightly modified solid phase synthesis chemistry to enable the ultra-large-scale chemical synthesis of biological oligomers and their use for multiplexing bioaffinity assays or for the generation of extremely large sequence-defined libraries. Oligopeptide synthesis at this scale enables the efficient development of epitope-specific antibodies and the characterization of protein function and protein-protein interactions relevant to cellular regulation and signalling. Applications of large-scale nucleic acid synthesis include aptamer research, gene expression analysis, gene assembly, DNA origami, spatial transcriptomics, digital information storage and many others. Approaches to large scale synthesis are now mostly limited to commercial services due to the complexity and proprietary nature of most biotechnological approaches. We propose to develop an open-source, table-top instrument capable of parallel synthesis of millions of unique sequences. This device will be a next-generation maskless array synthesizer, an optical engine that couples to a standard solid phase synthesizer and enables robust, easy and inexpensive access to ultra-large-scale synthesis, particularly of nucleic acid and peptides, but which will also facilitate the development of synthetic approaches suitable for other oligomers, such as oligosaccharides or engineered biomimetic constructs. To demonstrate the power and versatility of the highly efficient new device, we will (1) apply ultra-large-scale photolithographic nucleic acid synthesis for generating DNA libraries for archival digital data storage. In particular, we will show that ultra-large scale synthesis, in combination with efficient encoding, results in inexpensive and efficient molecular-level information storage and retrieval from DNA. In addition, in combination with our recently-developed photolithographic approach to RNA synthesis, we will (2) synthesize extremely large permutational libraries of RNA to comprehensively explore the binding affinity and fluorescence enhancement sequence landscape of the Mango family of fluorogenic RNA aptamers.
DFG Programme
New Instrumentation for Research
