Tuesday, March 27, 2012

Synthetic life and vitalism

Illustration courtesy of Harry Campbell
In 1966, Francis Crick—the co-discoverer of the structure of DNA—gave a series of lectures at the University of Washington in which he discussed vitalism and the nature of life (Crick, 1966). Vitalism is this old idea according to which some sort of special force is present in living organisms, and that this force cannot be explained in terms of physics and chemistry. Crick notes that a way to refute vitalism would be to create a living organism synthetically—in other words, make a cell from scratch. Crick's remark finds a striking echo in today's research in synthetic biology, particularly in the efforts of Craig Venter.

In 2010, Venter and his team from the J. Craig Venter Institute achieved a scientific tour de force: the synthesis of a whole bacterial genome (one circular chromosome) and its transplantation into a recipient cell (a mycoplasma). The resulting bacterium was able to grow and multiply thanks to its artificial chromosome. The results were announced during a press conference in May 2010 and published in Science two months later. The long-term goal of the JCVI is not to disprove vitalism, but to design and implant synthetic genomes that can perform specific tasks, such as to produce biofuels. The mycoplasma synthetic genome, which is only slightly different from the original, serves as a proof of concept, paving the way to more important genome (re-)engineering. 

Monday, March 19, 2012

Reporter bacteria to monitor arsenic concentration in groundwater

Vials containing bioreporter bacteria. Photo courtesy of UFZ.
It is not widely known, but analytical measurements with bacterial bioreporters can 
compete with commercially available detection kits, inasmuch as the bioreporters' efficiency (sensitivity, detection limit, etc.) is often comparable - if not better - than the chemical-based systems. So why are bioreporters not more widespread? Well, the leap from the laboratory to the field is a difficult one, which demands a tight collaboration between fundamental research and engineering. In addition, economical and policy challenges need to be overcome. Today, most developed bioreporters have never left the lab.

But this may change, and a recent study by Konrad Siegfried et al. published in Environmental Science & Technology is a remarkable demonstration of the usefulness of reporter bacteria in the field. [Among the authors of this paper are three scientists with whom I had the privilege to work: Antonis Chatzinotas and Hauke Harms from the UFZ in Leipzig and Jan Roelof van der Meer from the University of Lausanne (HH directed my master thesis and JRvdM directed my PhD thesis).]

In this study, the authors used a strain of E. coli that produces bioluminescence when it is exposed to arsenite and arsenate (oxidized forms of arsenic). Bacteria detect the poison thanks to a specific activator protein which binds arsenic and triggers the expression of specific genes. The result is the production of a set of proteins, including the bacterial luciferase, which makes the bacteria glow. 

Sunday, March 11, 2012

Jacques Monod and the origins of molecular biology

A beautiful model or theory may not be right; but an ugly one must be wrong. 
Jacques Monod 

 Published by ASM Press
After his work on bacterial growth, I'm now reading about Monod's later career and the discoveries that contributed to the creation of molecular biology. And for that purpose, I warmly recommend the revised edition of "Origins of molecular biology – A tribute to Jacques Monod", published at ASM Press. In this book, Agnes Ullmann and André Lwoff (two former collaborators of Monod) have compiled a collection of essays by colleagues and peers who recall their memories of the great scientist (among whom François Jacob, Francis Crick, Salvador Luria and many others). The book should be praised for providing a mosaic view that tells both the story of the science and the story of the man. And what a man! Bacterial growth kinetics, messenger RNA, enzymatic repression, lac operon, allosteric proteins… A Nobel prize received in 1965 (together with André Lwoff and François Jacob) rewarded their «discoveries concerning the genetic regulation of enzyme and virus synthesis». But, although the book portrays Jacques Monod as an extraordinary man and a great scientist, this is no hagiography, and the darker sides of his personality are evoked as well. 

Thursday, March 01, 2012

The mechanics of bacterial cluster formation on plant leaf surfaces as revealed by bioreporter technology

Green and red fluorescent bacteria on the surface of a leaf
Our new publication is out there as an early view in Environmental Microbiology, and I shamelessly take this opportunity to write about it here!

Here's the story. The plant foliage is colonized by a crowd of microbes (with bacteria on the front line—up to 108 bacteria per gram of leaf has been reported!). Some of them can be pathogenic, hence a threat, but most of them are harmless or even favorable inhabitants of the plant ecosystem.

Bacteria form large clusters (aggregates) of cells on the surface of leaves, but the mechanism of formation of such structures is not very well understood. What we want to know is how these bacteria grow and colonize this specific environment at the microscale, that is, at their own scale.

First, bacteria have to land on the leaf. Wind, rain, insects can all contribute to bring microbial visitors onto the leaf surface (what we call the phyllosphere), usually few cells at a time. Once on the leaf, these immigrants will grow at the expense of the plant sugars available on the leaf and, if the conditions are favorable, rapidly multiply to form clusters of up to thousands of cells. Do these clusters result from the random aggregation of cells or do they result from the reproduction of a single bacterium? The two mechanisms—that we call aggregative and replicative—are fundamentally different but not necessarily mutually exclusive. 

Thanks to fluorescence microscopy it is possible to visualize glowing bacteria on the surface of a leaf. One difficulty, however, is that we cannot follow the same microarea of leaf overtime… We are limited to a snapshot view, and so it's impossible to decide whether a given cluster was formed through aggregative or replicative behavior. For this reason we developed techniques that would enable us to deduce a posteriori what was the mechanism of formation.