Sequence space is defined by all the possible sequences of a given length. This space is extremely high dimensional. For example, an RNA molecule of length 25 has over 10¹⁵ unique sequences that make up the sequence space. If each sequence is assigned a relative activity, or "fitness", one can construct a Fitness Landscape, which are conceptual tools used to understand and predict the course of evolution. We are constructing real fitness landscapes for functional RNA molecules, using ribozymes as a model system. In order to determine the fitness of a very large number of sequences, we use next-generation seqeuncing technologies as an ultra-high throughput biochemical assay. Activites in the lab include assay development, library design, sequence analysis, data visualization and modeling.

Synthetic regulatory elements can be fabricated using RNA aptamers, which are short RNA sequences that bind specific molecular ligands. The logic of these systems is that binding of ligand by the RNA aptamer changes the structure of the RNA molecule in a way that alters gene expression. There are numerous challenges faced when applying these synthetic regulatory elements to mammalian systems. In collaboration with Dr. Ferguson, we are developing methods to watch these synthetic elements at work inside of living cells. This approach will provide data at new temporal and spatial scales that will be used to guide future designs.

Telomeres are repetitive sequences at the end of Eukaryotic chromosomes. They protect chromosomes from shortening at each cell division. Telomeres nevertheless shorten over time with age, and do so faster under stress. As such, they provide a unique non-invasive method for estimating the age and stress levels of individuals within a population. We are adapting protocols for non-model organisms, such as the Kestral, which is a small raptor studied in the Heath Lab.