Research Summary

My research focuses on understanding the relationship between genotype and phenotype, with a special interest in how biochemistry, molecular design, and wiring can allow cells to process information from their environment and respond appropriately. By comparing similar pathways in related species and duplicated genes in the same species we can study the importance of quantitative features of pathways.

Why have 10% of yeast genes been preserved in duplicate? By swapping the promoters and coding regions of a number of duplicate genes and monitoring both transcription and fitness we will determine which quantitative features of duplicate genes are required.

Does over-expressing a protein increase the total protein abundance in a cell or decrease the expression of every other protein? How much can a protein level be varied before we observe phenotypic/fitness costs? How similar are environmental responses in related yeast species? How easy is it to evolve quantitative features of signaling pathways? Where does most of the functionally relevant evolution happen: mRNA abundance, protein level, post-translation modification, etc.? To address these and other related questions, we are focusing on cellular homeostasis, beginning with pH homeostasis. We mainly use fluorescence read-outs in response to the environment in different wild-type and mutant backgrounds to build quantitative data sets appropriate for numerical and analytical approaches.

Selected References

A general lack of compensation for gene dosage in yeast. Springer M, Weissman J, Kirschner M. Submitted.

Need-based up-regulation of protein levels in response to deletion of their duplicate genes. De Luna A*, Springer M*, Kirschner M, Kishony, R. Submitted.

BioNumbers – the database of key numbers in molecular biology. Milo R*, Jorgensen P*, Weber G, Springer M. Submitted

Singh S*, Springer M* , Steen J, Kirschner M, Steen H,. FLEXIQuant: A novel tool for the absolute quantification of proteins , and the simultaneous identification and quantification of modified peptides. Journal of Proteome Research 2009 8 May; (5) 2201-10.

*Contributed equal.