This project is jointly funded by the Chemistry of Life Processes Program in the Division of Chemistry, and the Genetic Mechanisms and Systems and Synthetic Biology Clusters in the Division of Molecular and Cellular Biosciences.

Life is thought to have emerged on the early earth as a consequence of the chemistry of the young planet. Subsequently, there was assembly into simple cells that could grow, divide and evolve. Such cells were probably composed of a cell membrane that enclosed a primitive version of RNA that could store useful information and also carry out simple cellular functions. At present, there is a lack of a full understanding of how genetic materials such as RNA could have been copied before the evolution of enzymes. This project involves a series of experiments aimed at achieving fast and accurate non-enzymatic copying of short RNA strands. The ability to copy RNA in a purely chemical manner is an essential step towards the goal of assembling simple living cells from inanimate chemicals. This in turn would contribute greatly to our understanding of the origin of life on the early earth, and to assessing the likelihood that life might exist on other planets. Since the Origin of Life and the search for life in the Universe are topics of great public interest, this work contributes to public engagement with science as well as to the training of many young scientists.

This project involves experimental studies aimed at attaining a better understanding of the chemical reaction mechanisms involved in non-enzymatic template-directed RNA replication. The methodology involves modern structural methods such as X-ray crystallography and NMR spectroscopy, together with reaction kinetics and molecular modeling. In addition, modified nucleotides that may have been present on the early earth and that may lead to faster and more accurate copying of RNA templates are being synthesized and characterized. The project also includes investigations of high energy chemical compounds that could have supplied the energy needed to drive RNA replication. The ability to chemically replicate RNA molecules that are long enough to encode ribozyme catalysts would help in understanding how very simple living cells could be reconstituted from individual chemical components.

Agency
National Science Foundation (NSF)
Institute
Division of Chemistry (CHE)
Type
Standard Grant (Standard)
Application #
1607034
Program Officer
Max Funk
Project Start
Project End
Budget Start
2016-09-01
Budget End
2021-08-31
Support Year
Fiscal Year
2016
Total Cost
$1,000,000
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Somerville
State
MA
Country
United States
Zip Code
02145