Single cell gene expression linkfest

Gene regulation is an old field, but gene regulation at the single cell level is a whole new ball of wax. Some of us in the lab are trying to get up to speed in this field, and I need to pick out five good papers for consideration.

The place to begin is with this great review, and then work through the references:

Central dogma at the single-molecule level in living cells, Gene-Wei Li and X. Sunney Xie, Nature 475, 308–315 (21 July 2011)

Picking selectively, I ended up with the list below, and unfortunately I need to somehow narrow this down to five… and preferably all five won’t be from Sunney Xie’s group. Any suggestions?

Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells, Yuichi Taniguchi, Paul J. Choi, Gene-Wei Li, Huiyi Chen, Mohan Babu, Jeremy Hearn, Andrew Emili and X. Sunney Xie, Science 30 July 2010: Vol. 329 no. 5991 pp. 533-538 Continue reading “Single cell gene expression linkfest”

Don’t ask a biologist to explain the behavior of the solar system

After reading a string of disheartening reviews on the supposedly important future directions of biological research, I’m convinced that the older generation of biologists, those who made their careers in heyday of molecular biology during the 60’s, 70’s, 80’s, have turned biology into an innumerate outlier among the natural sciences. Continue reading “Don’t ask a biologist to explain the behavior of the solar system”

The genome is a huge haystack. How do you find the needle?

The complexity of the machinery by which our cells run is so extreme that one of the key questions in biological research is, why doesn’t the whole thing just collapse like a house of cards in a tornado? Another way of phrasing this question is to ask, where does the information come from to keep everything running smoothly?

Consider this: the crucial task of gene regulation is carried out in large part by transcription factors, regulatory proteins that recognize and bind to very short, degenerate DNA sequences located somewhere in the rough (sometimes very rough) vicinity of genes. Once they bind, transcription factors recruit the machinery that activates their target genes. (You can also have transcription factors that repress target genes.) This is all good, until you consider the fact that a human transcription factor has to find its target sequences from among the 3 billion base pairs in the human genome. Some plant and fish transcription factors have to search through genomes with more than 100 billions base pairs. So the question is, why don’t transcription factors get lost? Where are they asking for directions?

On finding needles in the genomic haystack Continue reading “The genome is a huge haystack. How do you find the needle?”

Confusing data with theory

Maybe because experiments can be so much work, molecular biologists are just happy to have the data:

Krakauer, et al. “The challenges and scope of theoretical biology”, Journal of Theoretical Biology Volume 276, Issue 1, 7 May 2011, Pages 269–276:

The current absence of a strong theoretical foundation in biology means that there is weak guidance regarding what quantities or variables need to be understood to best inform a general understanding (an explanatory basis) for biological features of interest. An unfortunate result of the absence of theory is that some researchers confuse just having data with ‘understanding’. For example there is a base for collecting and analyzing the most microscopic data: experimental procedures and measurements in a high-throughput transcriptomics study are built around the assumption that transcripts are the primary data to be explained, and in neuroscience, recording from numerous individual neurons. This bias reflects a rather naive belief that the most fundamental data provide a form of explanation for a system, as if enumerating the fundamental particles were equivalent to the standard model in physics.

And here is this kind of thinking in action:

Nurse and Hayles. The cell in an era of systems biology. Cell (2011) vol. 144 (6) pp. 850-854: Continue reading “Confusing data with theory”

Progress in biology?

“I came to work at the MRC Unit for the Study of Structure of Biological Systems in September of 1951…The then tiny unit, composed of Max Perutz, John Kendrew, Francis Crick, and Hugh Huxley, with Sir Lawrence Bragg, the Cavendish Professor, as its very involved patron, had as its objective the understanding of life at its deepest level, the molecular. By so doing, they hoped to transofrm biology from a morass of seemingly limitless and often boring facts into an intelectually satisfying discipline like physics and chemistry.”

– James Watson, “Minds That Live For Science”, in A Passion for DNA.

60 years later:

“Biology is entering a period where the science can be underlaid by explanatory and predictive principles, rather than little bits of causality swimming in a sea of phenomenology.”

– Eric Davidson, quoted in Erica Check Hayden,”Life is Complicated,” Nature April 1, 2010

Will we ever escape from the morass of limitless, boring facts?

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