Lee Lab publish in Cell Systems
NF-𝛋B Dynamics Discriminate between TNF Doses in Single Cells
Zhang Q1, Gupta S1, Schipper DL, Kowalczyk GJ, Mancini AE, Faeder JR, Lee REC*
Using an information theory framework and single-cell data, Zhang et al. set out to distinguish between different mechanisms for activation of intracellular signals. They show that heterogeneity between cellular states can lead to underestimates in the capabilities of single cells. In contrast with a switch-like model for pathway activation, they find that single cells can encode multiple levels of response that increase with stimulation strength.
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The Xing lab published a research article in FEBS Letters.
miRNAs serve as crucial post-transcriptional regulators in a variety of essential cell fate decisions. However, the contribution of the mRNA-miRNA mutual regulation to bistability is not fully understood. Here, we built a set of mathematical models of mRNA-miRNA interactions and systematically analyzed the sensitivity of the response curves under various conditions. Our findings indicate that mRNA-miRNA reciprocal regulation could manifest ultrasensitivity to subserve the generation of bistability when equipped with a positive feedback loop. We also find that the region of bistability is expanded by a stronger competing endogenous mRNA (ceRNA). Interestingly, bistability can be generated without a feedback loop if multiple miRNA binding sites exist on a target mRNA. Thus, we demonstrate the importance of simple mRNA-miRNA reciprocal regulation in cell fate decisions.
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Tian X-J, Zhang H, Zhang J, Xing J (2016) Reciprocal Regulation Between mRNA and miRNA Enables a Bistable Switch That Directs Cell Fate Decisions FEBS Letters doi: 10.1002/1873-3468.12379.
“Crosstalk Between Toll-like Receptor Pathways”
A collaboration between the Bahar lab, the Ding lab (National Singapore University), and the Thiagarajan lab (Harvard), led by Dr. Liu in the Bahar lab.
Toll-like receptors (TLRs) recognize pathogens and stimulate the innate immune response. Liu et al uncovers how the crosstalk between TLR pathways enables macrophages to fine-tune their responses to multiple infection events. In particular, macropahges can “memorize” the first pathogen attack and boost the immune response to subsequent attacks. The crosstalk also helps to avoid the harmful excessive inflammatory responses.
Clark and Chikina publish their study of Marine Mammal Evolution in Molecular Biology and Evolution. One of the authors was their former TECBio REU student, Joe Robinson. Congrats to everyone!
Mammal species have made the transition to the marine environment several times, and their lineages represent one of the classical examples of convergent evolution in morphological and physiological traits. Nevertheless, the genetic mechanisms of their phenotypic transition are poorly understood, and investigations into convergence at the molecular level have been inconclusive. While past studies have searched for convergent changes at specific amino acid sites, we propose an alternative strategy to identify those genes that experienced convergent changes in their selective pressures, visible as changes in evolutionary rate specifically in the marine lineages. We present evidence of widespread convergence at the gene level by identifying parallel shifts in evolutionary rate during three independent episodes of mammalian adaptation to the marine environment. Hundreds of genes accelerated their evolutionary rates in all three marine mammal lineages during their transition to aquatic life. These marine-accelerated genes are highly enriched for pathways that control recognized functional adaptations in marine mammals, including muscle physiology, lipid-metabolism, sensory systems, and skin and connective tissue. The accelerations resulted from both adaptive evolution as seen in skin and lung genes, and loss of function as in gustatory and olfactory genes. In regard to sensory systems, this finding provides further evidence that reduced senses of taste and smell are ubiquitous in marine mammals. Our analysis demonstrates the feasibility of identifying genes underlying convergent organism-level characteristics on a genome-wide scale and without prior knowledge of adaptations, and provides a powerful approach for investigating the physiological functions of mammalian genes.
Maria Chikina, Joe Robinson, Nathan Clark. “Hundreds of genes experienced convergent shifts in selective pressure in marine mammals.” Molecular Biology and Evolution. 2016.