Scialog: Collaborative Teams - 2016
Conditional Gene Essentiality as Function of Cell Metabolic State
It is basic knowledge in biology that the interaction of an organism’s set of genes (its genotype) with the environment results in that organism’s set of observable characteristics (its phenotype). But beyond this point there are many questions that scientists have yet to answer.
Systems biologist Kimberly Reynolds (UT Southwestern) and theoretical biophysicist Adilson Motter (Northwestern) have teamed up to investigate uncharted territory in this area with the help of an innovative Scialog Award ($50,000 each) that encourages cutting-edge research.
Reynolds and Motter’s investigation will attempt to determine if the order in which genes are “knocked out” (deleted) from an organism has any influence on its resulting phenotype. Current thinking is that knockout order does not play a role in the resulting characteristics of an organism.
To look for answers they will repeatedly knock out different enzyme-coding genes in the closely studied bacterium Escherichia coli (specifically E. coli K12 MG1655). In creating these variations in the bacterium, the researchers also hope to learn what defines a cell state under a given condition, and whether the loss of fitness caused by a gene knockout can be systematically recovered by knocking out additional genes.
If successful, their experiments could lead to a new understanding of the essential nature of genes and, ultimately, to refinements in how genetic modifications may be performed in many different types of organisms from plants to humans.
Reynolds and Motter are among more than 60 early career scientists participating in Scialog: Molecules Come to Life, a three-year program jointly sponsored by Research Corporation for Science Advancement (RCSA) and the Gordon and Betty Moore Foundation. Additional funding has been provided by the Simons Foundation. Scialog supports research, intensive dialog and community building to address scientific challenges of global significance. Within each multi-year initiative, Scialog Fellows collaborate in high-risk discovery research on untested ideas and communicate their progress and form new collaborations in annual conferences.
Molecules Come to Life focuses on such questions as, what are the fundamental principles that make a collection of molecules within a cell produce behaviors that we associate with life? How do molecules combine and dynamically interact to form functional units in cells, and how do cells themselves interact to form more complex lifeforms?
The researchers formed their collaboration at a Scialog conference held earlier this year in Tucson, Arizona. There scientists from diverse fields of biology, physics and chemistry engaged in intensive discussions designed to produce creative ideas for innovative research.
“Scialog aims to encourage collaborations between theorists and experimentalists,” said RCSA Program Director Richard Wiener. “And, we encourage approaches that are driven by theory and coarse-grained modeling, that are testable by experiments.”