Change Tan

Assistant Professor of Biological Sciences

PhD, 2000 University of Pennsylvania

tanc@missouri.edu
573-882-1581
340B Christopher S. Bond Life Sciences Center

Research description

Novel means of generating conditional mutations
A major focus of our laboratory is to generate novel genetic tools to determine gene function. We have developed an intein switch that allows for the conditional ablation of protein functions and is applicable to a wide range of model organisms. This intein switch is based on a temperature sensitive (TS) intein. An intein is a polypeptide embedded within a precursor protein that excises itself autonomously to generate a wild-type functional protein. Our TS intein splices only at low temperatures. Failure to splice at high temperatures ablates protein function. Thus loss-of-function is easily mediated via a temperature shift. We are currently using this switch to perform a genome-wide screen in Drosophila melanogaster.

We are interested in making our conditional mutagenesis approach amenable for use in endotherms, such as mice. To achieve this we are developing a destabilizing intein switch that excises only in the presence of a small molecule. We envision using this switch to generate a genome-wide collection of conditional mutations in mouse embryonic stem cells.

Mechanism of incomplete cytokinesis during gametogenesis
Our lab is also interested in studying the mechanism of incomplete cytokinesis during gametogenesis. Incomplete cytokinesis is a special kind of cytokinesis and a hallmark of germline stem cell differentiation. Incomplete cytokinesis is a nearly universal process during spermatogenesis; and plays an essential role in oogenesis in Drosophila, humans and other species. Incomplete cytokinesis occurs when the cleavage furrow fails to close completely during cell division. Resulting daughter cells remain interconnected via the cleavage furrow that is subsequently modified and becomes a ring canal. The mechanism mediating arrest of cleavage furrow constriction is unknown. Non-muscle myosin II is the driving force of cleavage furrow constriction. We hypothesize that myosin phosphatase inhibits myosin II thus arresting constriction. We are currently testing this hypothesis. By elucidating the mechanism of incomplete cytokinesis in Drosophila, we hope to further our understanding of gametogenesis and stem cell differentiation, as well as to gain insight into infertility pathologies.

Selected publications

Tan, G, Chen, M, Foote, C, and Tan, C. 2009. Temperature-sensitive mutations made easy⎯ Generating conditional mutations by using TS-inteins that function within different temperature ranges. Genetics.

Ong, S, and Tan, C. 2009. Germline cyst formation and incomplete cytokinesis during Drosophila melanogaster oogenesis. Dev. Biol.

Wang, Y, Tan, C (co-first author), Fagan, RJ, and Klein, PS. 2006. Phosphorylation of frizzled-3. J Biol Chem. 281(17): 11603-9.

Zeidler, M, Tan, C (co-first author), Bellaiche, Y, Cherry, S, Häder, S, Gayko, U, and Perrimon, N. 2004.Temperature-sensitive control of protein activity by conditionally splicing inteins. Nature Biotechnol. 22(7): 871-6 (with cover).

Tan, C, Stronach, B, and Perrimon, N. 2003. Myosin phosphatase plays multiple roles in Drosophila development. Development 130(4): 671-81.

Deardorff, MA, Tan, C (co-first author), Conrad, LJ, and Klein, PS. 1998. Frizzled-8 is expressed in the Spemann organizer and plays a role in early morphogenesis. Development 125(14): 2687-7000.

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