The Systems Biology of Gene Expression Section in the National Cancer Institute was established in February, 2011. During that time, the primary goal has been to build a cellular biophysics laboratory for interrogating gene expression in single cells. A custom fluorescence microscope was designed, and the initial parts were purchased. The microscope consists of a Zeiss AxioObserver inverted microscope stand coupled to multiple Newport single-mode lasers. The microscope stage is a custom stage built in collaboration with Mad City Labs for real-time single molecule tracking. The cameras are EMCCD cameras from Andor. The microscope is optimized for photon collection sensitivity and low drift. The mechanical construction of the microscope is still in the early days. However, much of the control and analysis software was written during this past year using the IDL programming language. Also during the last year, Murali Palangat, Ph. D. was recruited as a lab biologist. Dr. Palangat has extensive experience with transcription in both prokaryotes and eukaryotes and has a superb track record in developing single-molecule biophysical assays for RNA polymerase II. Dr. Palangat has published a number of papers in leading journals demonstrating the connection between polymerase elongation and gene regulation. He developed an in vitro single molecule preparation for mammalian RNA polymerase which has become the enabling technology for labs around the world. He is uniquely qualified for the position in that he is intimately familiar with transcription and gene regulation, appreciative of the nuances of single-molecule studies, and also practiced at operating and managing a biophysical laboratory. During the summer of 2011, Celine Hong was a summer intern in the section. During her time in the lab, she carried out a meta-analysis on two recently published data sets on breast cancer gene regulation. This work leads to direct predictions about the functional significance of co-regulation of genes during estrogen signaling. The testable hypotheses generated from this bioinformatic analysis will form the basis of several experimental efforts in the section in the next fiscal year.
| Patange, Simona; Girvan, Michelle; Larson, Daniel R (2018) Single-cell systems biology: probing the basic unit of information flow. Curr Opin Syst Biol 8:7-15 |
| Wan, Yihan; Larson, Daniel R (2018) Splicing heterogeneity: separating signal from noise. Genome Biol 19:86 |
| Das, Satarupa; Parker, Joshua M; Guven, Can et al. (2017) Adenylyl cyclase mRNA localizes to the posterior of polarized DICTYOSTELIUM cells during chemotaxis. BMC Cell Biol 18:23 |
| Hendy, Oliver; Campbell Jr, John; Weissman, Jocelyn D et al. (2017) Differential context-specific impact of individual core promoter elements on transcriptional dynamics. Mol Biol Cell 28:3360-3370 |
| Ren, Gang; Jin, Wenfei; Cui, Kairong et al. (2017) CTCF-Mediated Enhancer-Promoter Interaction Is a Critical Regulator of Cell-to-Cell Variation of Gene Expression. Mol Cell 67:1049-1058.e6 |
| Chen, Huimin; Larson, Daniel R (2016) What have single-molecule studies taught us about gene expression? Genes Dev 30:1796-810 |
| Lenstra, Tineke L; Rodriguez, Joseph; Chen, Huimin et al. (2016) Transcription Dynamics in Living Cells. Annu Rev Biophys 45:25-47 |
| Lenstra, Tineke L; Larson, Daniel R (2016) Single-Molecule mRNA Detection in Live Yeast. Curr Protoc Mol Biol 113:14.24.1-14.24.15 |
| Coulon, A; Larson, D R (2016) Fluctuation Analysis: Dissecting Transcriptional Kinetics with Signal Theory. Methods Enzymol 572:159-91 |
| Palangat, Murali; Larson, Daniel R (2016) Single-gene dual-color reporter cell line to analyze RNA synthesis in vivo. Methods 103:77-85 |
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