Xenobiology Lab - Marchand Group

Propelling XNAs to the modern sequencing era. Many modern molecular biology and synthetic biology workflows rely on next generation sequencing for evolution, analysis, and manipulation. However, modern nucleic acid sequencing technology was built for 4-letter DNA, and is therefore unable to read XNA letters. As a general solution, our group is teaching nanopore sequencers how to read XNA letters using advanced machine learning strategies (e.g., neural networks) and 'big-data omic' approaches.

Harnessing XNAs for advancements in diagnostics and environmental surveillance. Nucleic acids are a key component for many diagnostic and surveillance applications. XNAs have the potential to radically improve existing nucleic acid assays and have already seen commercial success. As a prime example, XNAs are a critical component in some commercially available RT-qPCR SARS-CoV2 diagnostic assays. Towards this area of application, our group is exploiting the chemical diversity that the non-standard XNA letters provide to develop more sensitive, specific, cost-efficient, and multiplexable nucleic acid assays.

Engineering organisms for next-generation synthetic xenobiology. Life evolved around using the standard, 4-letter DNA alphabet (ATGC) for biological information storage. Expanding the genetic alphabet of life with XNA building blocks would allow novel synthetic biology applications, including: genetic code expansion beyond 64 codons, novel regulatory mechanisms based on XNA logic gates, and biocontainment strategies. Our lab is genetically engineering bacteria that will be compatible with an expanded alphabet composed of 6 or more letters (ATGCXY).

Enzymatic synthesis and biosynthesis of XNAs. XNAs, and their associated building blocks, are currently made through expensive, time consuming, organic syntheses. Our group seeks to eliminate barriers to performing XNA research by leveraging enzymatic and biosynthetic approaches. To eliminate barriers associated with synthesis of XNA sequences, we investigate novel strategies that leverage enzymes to site-specifically insert XNA base pairs into DNA. To endow organisms the ability to make their own XNAs, we turn to Nature - and explore how to co-opt enzymes from nucleoside natural product biosynthesis.