Research

Genetically identical individuals are never phenotypically identical even in the same environment. How does this non-genetic, phenotypic diversity arise and what are its consequences for the survival of the individual and the population? What mechanisms are used by organisms to reduce or exploit this diversity? These are fundamental questions in evolution, organismal development and disease.

The Lim Lab examines how genetic systems regulate phenotypic diversity in genetically identical populations. Our work integrates mechanisms at the molecular, cellular, population and ecological levels using Escherichia coli as a model system. We use a combination of theoretical and experimental approaches to identify general mechanisms for generating diversity in biological systems. This knowledge may help to develop better strategies to combat bacterial infections.

Current projects:

1. Noise in genetic circuits and its role in cell survival. Random fluctuations that occur during the creation and destruction of molecules are often considered to be an unavoidable nuisance that must be minimized in order to increase the efficiency of cellular processes. However there is also evidence that cells can design their genetic circuits to harness this noise to generate diversity in the population as a strategy to survive and/or more rapidly adapt to environmental changes. We are examining the molecular mechanisms used by organisms to reduce or exploit noise in genetic circuits and its implications for evolution, organismal development and disease.

2. Epigenetic control of gene regulation. DNA methylation is able to turn gene expression on or off and it enables these expression states to be inherited from mother to daughter cell for many generations ('epigenetic memory'). We are studying the mechanism of transcriptional regulation by DNA methylation and how organisms incorporate epigenetic memory into their long-term decision-making.

3. Information processing at cis-regulatory sequences. The cis-regulatory sequences located upstream of the coding sequence are the primary site of regulatory control in genetic circuits. A major project in the lab is focused on devising strategies to systematically identify functional elements in the cis-regulatory region and their interactions. From this information we are creating "circuit diagrams" that provide a detailed understanding of how gene expression is controlled and can be used to rationally re-engineer synthetic promoters that produce novel outputs.

4. RNA circuits. It is increasingly recognized that small RNAs have an important role in intracellular signaling in many organisms. In bacteria, small RNAs act on target gene RNAs by increasing their destruction and/or increasing and decreasing translation. We are comparing the signaling properties of RNA in genetic circuits and constructing synthetic RNA based circuits for biotechnology applications.