Protein Sociology: Collective Interaction Behaviors |
As always, it’s these odd conjunctions of things that don’t go together that catches the eye. In this case, molecular and sociology. The actual article1 is much more mundane and true to the correct science jargon, and included in a special section of the most recent Nature on “Proteins to Proteomes.” It’s also a nice article that examines a broad array of topics in molecular biology.
Of greater interest and with a slightly less catchy title, is another article on the section: Reaching for high-hanging fruit in drug discovery at protein–protein interfaces2. The abstract: (more…)
Battling Disease – The Real-Life Hydra? |
A recent article in Science discussed a claim made by Bill and Melinda Gates, where they proposed that malaria could be eradicated from the Earth over the next few decades. Vanquishing disease is seen as the ultimate goal in medical science, and many dream of the day that we will all be living longer and healthier lives. But the real question is, how do you beat something that will always outrun you? (more…)
Thinking Microbes |
Cognition is a term frequently used in several loosely related ways to refer to a faculty for the human-like processing of information. Signal transduction networks certainly fit that bill, as the mediate adaptive changes in gene expression to specific sensory inputs. Melinda Baker and Jeffry Stock, in the recent issue of Current Biology, elaborate on modalities of such cognition in bacteria: Networks and integrated circuits in bacterial cognition.
Of course, they’re not quite circuits in the electrical engineering sense either. Think chemical networking, where each biomolecule in a signaling network can interact with a variety of other molecules, with varying interaction kinetics, and where each interaction has the potential to impact additional outcomes. Coupled with the selection of functions in the micro-environmental milieu, cellular networks ended up organized in efficient ways to control motility, metabolism, growth, and eventually higher processes.
But just suppose for a moment that a cell, even a bacterium, didn’t merely process inputs from the micro-environment. Some people suggest that the information processing, regulatory feedback loops, and adaptive response to stimuli, constitute something else: (more…)
Myosin Isoforms: Duplication and Divergence |
Myosin II functions as a molecular motor which facilitates contraction of the actin cytoskeleton during migration, resides outside of protrusions at the front of motile cells, and acts at a distance to impact cell protrusion, signaling, and maturation of nascent adhesions. So clearly myosin II is a protein that is of great importance for understanding cell migration.
But Myosin II is not just one protein. There are actually two isoforms of this protein that are not identical, just very very similar. I’m not familiar with where in the natural history of cells the genes for these two proteins diverged, but they’re clearly derived from a single ancestral gene. And beyond that, there are quite a few other myosins which are more distantly similar (the list easily goes into double-digits)1.
Vicente-Manzanares et al.2, in their paper, determine the divergent functions of myosin IIA (MIIA) and MIIB, and find that these isoforms have become suited to spatial and functional niches within the cell. They found: (more…)
miRNAs Get Flipped |
On a couple other blogs, a study published in Science by Joan Steitz1 is being called “One of the biggest findings of the year,” and “If it turns out to be true, this finding just flipped the whole field on its head.” Bitesize Bio would be greatly remiss to not mention to so hot a story, joining in with The Daily Transcript and One Random Scientist.
The abstract, from Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation: (more…)
Entosis: Cellular Canabalism |
There might be more to cell death besides apoptosis and necrosis. In a paper that sounded a bit fishy to me, Michael Overholtzer, Joan Brugge and coworkers1 introduce “Entosis”: A non-apoptotic cell death process, that occurs by cell-in-cell invasion.
As Eileen White2 described:
Upon examination of mammary epithelial cell lines in suspension, Overholtzer et al. noticed the presence of cells within other cells. Further investigation of this phenomenon revealed that detachment of mammary epithelial cells from the ECM initiates a new pathway of nonapoptotic cell death called entosis in which one cell invades into another.
The Limits of Horizontal Gene Transfer |
Looking at the tree of life, descent with modification is an obvious theme, where genes are passed on through ‘vertical’ lines of ancestry. It so happens though that genes can jump from one lineage to another, by a process called ‘horizontal gene transfer’ (HGT). Naked DNA uptake (transformation), viruses (transduction), and plasmids (conjugation) are the mechanisms by which the genetic units of heredity need not be inherited in the usual sense. HGT appears to blur the boundaries of what a species is, particularly for the bacterial domain of life. So the study published by Rotem Sorek, Edward Rubin et al.1 on the determination of barriers to HGT is interesting from a couple different perspectives. (more…)
The Biased Choices of Cells |
Here’s one of my favorite journal articles from the past year – an elegant study by Natalie Andrew and Robert Insall published in Nature Cell Biology: Chemotaxis in shallow gradients is mediated independently of PtdIns 3-kinase by biased choices between random protrusions. From the introduction:
We have made detailed, quantitative observations of Dictyostelium cells chemotaxing in shallow gradients, which contradict current models in several ways (see Supplementary Information, Fig. S1): first, new pseudopods are made in spatially restricted sites by splitting of the leading edge; second, the timing and direction of these new pseudopods are random, so they cannot correct the cell’s direction; and third, the survival and retraction of pseudopods are spatially controlled, suggesting an alternative mechanism of chemotaxis.
This model is very similar to the mechanism of growth cone guidance, where random protrusions are constantly exploring the cell’s surroundings, ‘tasting’ for attractant or repellant cues. These cues either stabilize or destabilize one side of the growth cone or pseudopod over the other side, causing the cell to turn one way or another. This isn’t a new concept (having been addressed in neutrophils previously – Arrieumerlou and Meyer, 2005), but Andrew and Insall formalize the case for biased choices in chemotaxis in Dictyostelium very nicely (Figure 1, below).
Ribosomal Paralogs not Redundant Afterall |
In the budding yeast Saccharomyces cerevisiae, 59 of the 79 cytoplasmic ribosomal proteins are encoded by two genes, stemming from an ancient genome duplication event. Komili et al. (2007) now report that these paralogous genes are not functionally equivalent, suggesting the possible existence of a �ribosome code.�1
Yeast and mammalian genomes are riddled with apparently duplicated genes, differing in only a few amino acids from one paralogue to its clone. Because they’re so nearly identical, most researchers assume some degree of redundancy in such circumstances, and attempt to ascertain the function of only one of the two. If there is any difference in function between two paralogues, the difference might be unimportant, or just too difficult to tease apart experimentally.
As we gain more and more insight into how the cell works, such minutiae might be a curious area to study up on. In the case of the yeast S. cerevisiae, it turns out that 59 of their 78 ribosomal proteins have doubles that differ by only a few amino acids. Suzanne Komili, Pamela Silver (Harvard Medical School, Boston, MA), and colleagues2 make an intriguing argument that only rarely are individual members of a paralogous gene pair functionally identical, despite this strong sequence similarity. (more…)
Microtubules at the Membrane in Apoptosis |
Apoptosis, or programmed cell death, is an evolutionarily conserved and neatly orchestrated process important for tissue remodeling and safe elimination of severely damaged cells. Conducted by a caspase-mediated proteolytic cascade, the cell death program results in a series of cellular changes distinct from cellular necrosis. And one of the critical aspects that distinguish apoptosis from necrosis is that intracellular components of apoptotic cells are isolated, preventing membrane permeability and release of inflammatory molecules.
Just how do dying cells keep themselves from spilling out their materials into the surrounding tissues? And what role do the cytoskeleton components have in this process? Those are the questions that Jos?© S??nchez-Alc??zar and colleagues1 asked in a paper in July’s issue of the journal Apoptosis. (more…)