Lila M. Gierash

Lila M. Gierasch pioneered biophysical studies of signal peptides, the N-terminal sequences that direct proteins for secretion across membranes. Using synthetic peptides and spectroscopic methods, she established how these hydrophobic targeting sequences interact with lipid bilayers and protein translocation machinery, revealing conformational features required for function.

At the University of Delaware, Gierasch synthesized signal peptides corresponding to the Escherichia coli LamB protein and characterized their behavior using circular dichroism, NMR spectroscopy, infrared spectroscopy, and monolayer techniques. Her studies demonstrated that functional signal sequences adopt α-helical conformations when inserted into lipid environments, while interaction with lipid surfaces without insertion induces β-structure. Export-defective mutant signal peptides showed reduced helical propensity and diminished membrane affinity.

These findings, published in Science in 1985 and 1986, established that signal peptides are not merely passive tags but active participants in the secretion process. Gierasch proposed that conformational changes during membrane interaction facilitate the initial steps of protein export, a model that influenced subsequent understanding of the Sec translocation pathway.

Her research expanded to include interactions of signal peptides with SecA and the signal recognition particle, mapping binding sites through crosslinking and transferred NOE experiments. At the University of Massachusetts Amherst, where she held joint appointments in Chemistry and Biochemistry, Gierasch extended her interests to protein folding, chaperone function, and in-cell folding dynamics. She received the 2010 Dorothy Crowfoot Hodgkin Award from the Protein Society for exceptional contributions to protein science. Her laboratory demonstrated that turn sequences in proteins play active roles in folding nucleation, connecting decades of peptide conformational studies to protein folding mechanisms.