In all organisms, DNA is the matter of inheritance. As such, DNA provides the blueprint to build and operate each individual organism. Decoding the information contained in the DNA is thus a key process, termed ‘transcription’. Transcription needs to happen at the right time and in the right place, and deregulated transcription causes diseases such as cancers, diabetes, and developmental abnormalities. But how does a creature transcribe the specific DNA programs to develop a normal, functioning organ, or to adapt its life-style to a specific external influence?
My lab studies the so-called ‘Mediator’, a molecular machine that is required for transcription: without it, the information contained in DNA cannot be properly decoded. Intriguingly, several Mediator subunits are mutated in human diseases, including certain cancers and neurodevelopmental disorders, but how and why the Mediator mutations cause disease remains poorly understood.
Our mission is to define why and how Mediator function assures normal development, prevents sickness, and promotes healthy aging. We use the worm Caenorhabditis elegans and the house mouse as experimental animal models, because they share certain aspects of human biology, and because we can control their genetics. With this approach we dissect how individual Mediator subunits regulate lipid metabolism and fat storage, detoxification programs, organ development and differentiation pathways, and aging. By providing new insights into how DNA is transcribed, our investigations may lead to new diagnostics and/or therapeutics that can help cure human diseases.
MAJOR ACHIEVEMENTS & PUBLICATIONS
Ding W, Smulan LJ, Hou NS, Taubert S, Watts JL, Walker AK. s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways.. Cell Metab. 2015, pii: S1550-4131(15)00342-3. PMID: 26321661
Grants JM, Goh GY, Taubert S. The Mediator complex of Caenorhabditis elegans: insights into the developmental and physiological roles of a conserved transcriptional coregulator. Nucleic Acids Res. 2015, 27;43(4):2442-53. PMID: 25634893
Hou NS, Gutschmidt A, Choi DY, Pather K, Shi X, Watts JL, Hoppe T, Taubert S. Activation of the endoplasmic reticulum unfolded protein response by lipid disequilibrium without disturbed proteostasis in vivo. Proc. Natl. Acad. Sci. U.S.A. 2014, 111(22):E2271-80. PMID 24843123
Goh GYS, Martelli KL, Parhar KS, Kwong AWL, Wong MA, Mah A, Hou NS, and Taubert S. The conserved Mediator subunit MDT-15 is required for oxidative stress responses in C. elegans. Aging Cell. 2014, 13(1):70-79. PMID 23957350