Virus evolutionary ecology professor (and sometimes bacteria)
Queens College of the City University of New York
Currently working on SARS-CoV-2, Rotavirus, Lambda phage, Phi6, P. aeruginosa biofilms, M. tuberculosis phage therapy, gene expression noise, cellular event timing
| Lab | https://dennehylab.org/ |
| Google Scholar | https://scholar.google.com/citations?hl=en&user=xHV6zmQAAAAJ&view_op=list_works&sortby=pubdate |
Interestingly, noise in lysis timing did not significantly contribute to the noise in burst size and the burst size noise remained constant across different lysis times.
The most likely explanation for the experimentally observed constant burst size noise is that cell-to-cell differences in burst size originate from intercellular heterogeneity in cellular capacities to produce phages.
This may include non-random distribution of cellular components such as ribosomes or polymerases.
6/7
We found that lambda burst size first increased exponentially until saturating at longer lysis times. Burst size was positively correlated with cell size, but like Delbruck observed, burst size variation was much greater than variation in cell size. Burst size approached saturation at around 1,000 virions in 3 h, suggesting that burst size is not constrained lack of nutrients. Instead, spatial constraints may limit the number of phages that can be assembled.
5/7
Delbruck found that bacteria size varied by a factor of three, but burst size varied across three orders of magnitude.
Delbruck noted "Comparison with the distribution of bacterial sizes in the same culture shows that the wide distribution of burst sizes cannot be accounted for by variations in the size of bacteria alone."
What, if not cell size, explained the massive intracellular differences in progeny production?
This question has been largely unaddressed since Delbruck's time.
3/7
We revisited Delbruck's work and repeated his dilution technique to isolate single phage infected cells, but with a few key differences.
We used lysis-deficient phage lambda lysogens that can be thermally induced following a temperature spike. Once induced, these lysogens stop dividing, but will produce phage indefinitely until externally lysed with chloroform. The resulting progeny are able to form plaques on E. coli that express holin from a plasmid.
4/7
Our manuscript "Single-Cell Approach Reveals Intercellular Heterogeneity in Phage-Producing Capacities" is now available in Microbiology Spectrum: https://journals.asm.org/doi/epub/10.1128/spectrum.02663-21
We asked the question "What explains the huge amount of intracellular noise in virus progeny production?"
This question dates back to at least Delbruck's 1945 paper "The burst size distribution in the growth of bacterial viruses (bacteriophages)."
1/7