Lars Malmstroem, Ph.D.
About f1000
F1000 is a scientific literature awareness tool where selected researchers review and comment on current papers. I'm an associate member and hence can post reviews together with Ruedi Aebersold who is a full member. Please find my posts below.
2011-10-20: Phenotypic landscape of a bacterial cell.
This paper systematically screens 3979 knock-out strains of Escherichia coli over 324 conditions-for-growth phenotypes. This large dataset, which is available for download, is an invaluable resource for anybody interested in environmental perturbation/protein interactions.
This work describes a systematic study in which 3979 gene knockouts are tested in 324 conditions-for-growth phenotypes. The authors attempt to be as inclusive as possible in both relevant conditions and gene knockouts. This makes the resulting data set a unique resource for hypothesis generation. The simple readout of growth phenotype is surprisingly informative and is currently one of the few technologies accessible to studies of this magnitude where almost 1.3 million environmental perturbation/gene interactions were tested. Focused follow-up experiments where selected conditions are tested by more involved technologies such as transcript or proteomic analyses, will be easier to design and hence benefit from this study.
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2011-04-04: Second-order selection for evolvability in a large Escherichia coli population.
This paper shows that genomic epistasis plays a key role in evolution where initially favorable mutations alter the effect of subsequent synergistic mutations.
Fitness in bacteria can be evaluated by the competitiveness of one sub-strain among many under a certain condition. Descendants of the fittest bacteria will constitute the majority in a population after enough time has passed. In this paper, initially less-fit bacteria (eventual winner [EW]) would eventually achieve higher fitness than bacteria that were initially more fit (eventual loser [EL]). The authors prove that this is due to the fact that EL bacteria cannot benefit to the same degree as EW from a mutation in spoT. This paper convincingly shows that this is due to epistasis, where the genetic background of EL (specifically, in gene topA) does not benefit to the same extent as EW.
In other words, EW has a higher degree of evolvability or evolutionary potential compared to EL under the tested condition. This is an important finding with implications for, among other fields, directed evolution experiments, as early beneficial mutations might exclude parts of the evolutionary space where even more-fit bacteria could be possible.
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2011-01-19: The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA.
This important paper shows that the adaptive immune system of some bacteria can cut double-stranded DNA (dsDNA) sequences, and that the cut site is specified by a short nucleic acid sequence.
The 'clustered regularly interspaced short palindromic repeats' (CRISPR)/ CRISPR-associated (Cas) immune system of Streptococcus thermophilus can acquire specific CRISPR spacers from various sources, such as self-replicating plasmids. Plasmids that match these spacers are cut at a specific site determined by the spacer and produce blunt ends. The now linear plasmid is rapidly lost. This is important as this can be exploited by manipulating the CRISPR of bacteria so they cannot acquire plasmids that, for example, carry anti-biotic resistance genes. This paper also shows that the CRISPR/Cas system specifically cleaves dsDNA at specific sites. It is plausible that this system can also be exploited in the future to develop technology in which specifying where to cut DNA is as simple as synthesizing a matching CRISPR spacer.
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2010-10-26: Systematic analysis of human protein complexes identifies chromosome segregation proteins.
In this exciting work, high-throughput technologies were used to characterize protein complexes involved in chromosome segregation, and new members of these complexes were identified and verified.
Proteins organize into complexes to perform many cellular tasks. Knowledge about the composition and dynamics of these complexes will further the understanding of fundamental processes in biology. In this study, protein complexes involved in chromosome segregation were characterized using a combination of high-throughput imaging and immunoprecipitation (IP)-based mass spectrometry. Some of the more interesting finds were followed up and shown to be correct. The authors were able to use the genome-wide RNA interference (RNAi) screen (where testable hypotheses are difficult to generate) to identify potential targets, process all of them with high-throughput technologies and generate hypotheses that could be tested using traditional biochemical approaches. They tackled a well-studied system and came up with novel information.
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2010-04-27: Evolution of MRSA during hospital transmission and intercontinental spread.
Genome sequencing of methicillin-resistant Staphylococcus aureus (MRSA) from multiple temporal and spatial isolates has revealed information about infection paths and mutation rates.
Antibiotic-resistant bacteria are a growing global health problem. An obvious strategy to prevent the spread of such strains is to reduce transmission between individuals. This ultimately relies on our understanding of the transmission paths. In this paper, multiple strains were sequenced and single-nucleotide polymorphisms (SNPs) were analyzed in great detail generating a high-resolution dendrogram. The study demonstrates how genome sequencing of bacterial isolates (isolated across time and space) of a particular strain of MRSA, TW20, provides a high-resolution map on how bacteria spread between patients at the same hospital and provides information about intercontinental spread. The applied technology lays the foundation for investigating how the bacteria are spread long after the outbreak has occurred provided that a sufficient number of isolates were collected and catalogued.
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2010-01-13: Structure and mechanisms of a protein-based organelle in Escherichia coli.
In this study, X-ray structures of four microcompartment proteins that are the components of the protein-based organelle capsule explain how bent conformations are achieved and reveal an active gating function.
There is growing evidence that bacteria are, in fact, not devoid of internal compartmentalization but are rather highly organized. For example, bacterial proteins are to a large extent organized in protein complexes {1} and are sometimes localized to specific regions of the cytosol {2}; in addition, there is also evidence for protein-encapsulated organelles (see ref {3}, on which Ruedi Aebersold is an author). In this paper, Tanaka and colleagues reveal how one of the shell proteins has a bent conformation which allows these microcompartments to close. They also show that there is an active gate that presumably regulates the in- and out-flow of various molecular species. This paper adds to the evidence that the proteomes of bacteria are highly structured and compartmentalized.
References: {1} Kuehner et al. Science 2009, 326:1235-40 [PMID:16081736]. {2} Shapiro et al. Science 2009, 326:1225-8 [PMID:19965466]. {3} Kerfeld et al. Science 2005, 309:936-8 [PMID:19965468].
Check out the F1000 site for more information (need subscription) or pubmed for complete reference information.