Paper 1, due Week #6
In two pages (double-spaced) or less, describe the experiments (including controls, experimental techniques, and modeling techniques) that might have been done to justify the abstract. Students should not look up the original paper on the web. The point of the assignment is to determine what should have been in the paper.
Individual cells in genetically homogeneous populations have been found to express different numbers of molecules of specific proteins. We investigated the origins of these variations in mammalian cells by counting individual molecules of mRNA produced from a reporter gene that was stably integrated into the cell’s genome. We found that there are massive variations in the number of mRNA molecules present in each cell. These variations occur because mRNAs are synthesized in short but intense bursts of transcription beginning when the gene transitions from an inactive to an active state and ending when they transition back to the inactive state. We show that these transitions are intrinsically random and not due to global, extrinsic factors such as the levels of transcriptional activators. Moreover, the gene activation causes burst-like expression of all genes within a wider genomic locus. We further found that bursts are also exhibited in the synthesis of natural genes. The bursts of mRNA expression can be buffered at the protein level by slow protein degradation rates. A stochastic model of gene activation and inactivation was developed to explain the statistical properties of the bursts. The model showed that increasing the level of transcription factors increases the average size of the bursts rather than their frequency. These results demonstrate that gene expression in mammalian cells is subject to large, intrinsically random fluctuations and raise questions about how cells are able to function in the face of such noise.
A sample student response to this assignment is included below. All work is courtesy of an MIT student and used with permission. (PDF)
Paper 2, due Week #11
Paper for assignment #2: Zeng, L., S.O. Skinner, C. Zong, J. Sippy, M. Feiss, I. Golding. 2010. Decision making at a subcellular level determines the outcome of bacteriophage infection. Cell 141: 682–691.
In this assignment, students will write a critique of a published paper (Zeng et al. Cell 2010). The assignment should be written up like a referee report for a paper. The report should start with a paragraph that summarizes the work, and then critique the paper, considering the following questions:
- What experiments should be done?
- Are the conclusions supported by the experiments?