Institute for Cell Biology, University of Munich, Germany

Unexpected links between cellular organelles continue to unfold.

As a graduate student, I was intrigued by centrioles. Their beautiful ninefold symmetry, occurrence in pairs and positioning at the heart of the cell —as a constituent of the microtubule-organizing centrosome — made them appear significant. But how they are built and replicated, and even their true purpose in cell division, remained enigmatic.

Adding to my fascination was the fact that, in my cultured cells, one of the centrioles often acted as an anchor, or basal body, for a cilium-like appendage — even though the endothelial cells I used were not thought to ever have cilia.

Once considered a biological oddity, these stubby, non-motile 'primary' cilia are now known to be present in most cells of the human body (see here) and probably serve as essential sensors whose disturbance is linked to a growing list of diseases.

I have always wondered whether there is an additional functional link between centrioles and primary cilia. A recent paper (A. Robert et al. J. Cell Sci. 120, 628–637; 2007) shows that a protein involved in the biogenesis of primary cilia is also a bona fide constituent of the centrosome. Moreover, this centrosomal/ciliary component is tied into the regulation of the cell cycle.

This finding joins a series of recent discoveries of proteins that are both centrosomal and ciliary. Taken together, these studies are revealing a truly novel functional link: centrioles are there to make primary cilia; primary cilia act as sensors of external stimuli; and, as other studies have shown, external stimuli can regulate cell proliferation. So the mysterious organelles of my graduate student days are being demystified, but the story that unfolds turns out to be even more fascinating than I expected.

Posted by Brendan Maher at 07:58 PM | Permalink | Comments (0) | TrackBacks (0)

Max Planck Institute for Infection Biology, Berlin, Germany.

A microbiologist wonders how antimicrobial peptides beat infection.

My group is interested in why, although people often pick up infections and sometimes become ill, they almost always recover. Recovery is the result of a fantastically efficient immune system that relies in part on proteins and peptides that kill microbes.

Antimicrobial peptides were discovered in systematic searches for potential drugs, and there are several types. Most are cationic and bind to the anionic surface of microbes. Recently, Roberto Lande at the University of Texas in Houston and his colleagues convincingly showed that one antimicrobial peptide, LL-37, can also bind DNA and serve as an activator for other immune cells (R. Lande et al. Nature 449, 564–569; 2007).

LL-37 is one of several antimicrobial peptides that do more than kill microbes and activate immune cells. Its other functions include chemoattraction and wound repair. But, as its name indicates, LL-37 has only 37 amino acids. It is plausible that its multiple effects on the host are due to its interaction with specific receptors that, in combination with other signals, result in diverse biological functions. More intriguing, however, is the fact that LL-37 kills microbes in the first place.

The question is whether LL-37 and other antimicrobial peptides truly function as bacterial killing agents in the host. Their antimicrobial activity has so far been demonstrated only in vitro, where it might be a reflection of their cationic character. Another more attractive possibility is that infections are such an important threat to the host that, during evolution, many cationic proteins with diverse function were co-opted to serve as antimicrobial agents. If we do have many ways to kill microbes, maybe it is not so surprising that we often recover from infections.

Posted by Brendan Maher at 06:44 PM | Permalink | Comments (0) | TrackBacks (0)

University of Leicester, UK

A biochemist is excited by a universal glue for molecular biology.

Investigating the dynamic properties of proteins at the level of a single molecule allows insight into properties that are masked in ensemble studies. I have often found that the hardest part of such studies is immobilizing the molecule on a silica surface in a 'permanent' way that retains the molecule's function.

The proteins we investigate are usually prepared with a His-tag — comprising 6+ engineered histidine residues — that binds, via a chelated nickel ion, to nitriloacetic acid (NTA), aiding purification on an NTA affinity column. Immobilization through this tag would therefore be an attractive option. But alas, this is only partly successful using the standard NTA group because proteins have a significant probability of detaching from the silica support on the timescale of minutes.

But surely a chemist somewhere has improved on this technology? Thanks to Google, I found the work of Jacob Piehler who, in 2005, introduced tris-NTA, a cyclam ring with three groups attached to it. Tris-NTA shows a thousand-fold higher affinity for His-tags in the presence of nickel than NTA and a dissociation half-life of many hours.

Piehler and colleagues have gone on to exploit this technology as a general means of attaching fluorophores to His-tagged proteins and, most recently, as a convenient way of specifically conjugating proteins to streptavidin (A. Reichel et al. Anal. Chem. doi:10.1021/ac0714922; 2007).

The streptavidin-biotin complex is another widely-used 'glue' in biotechnology, but the use of an intermediate tris-NTA-biotin adaptor broadens its application to His-tagged proteins and renders the attachment reversible on addition of excess imidazole. I look forward to using this technology in our single-molecule studies, for which such a reversible glue has the same appeal as a Post-It note.

Posted by Brendan Maher at 10:42 PM | Permalink | Comments (0) | TrackBacks (0)

University of Arizona, Tucson, Arizona USA

An ecologist wonders how biotic feedback matters to global-change research.

I have increasingly been drawn to the question of how the biotic world responds to climatic change. In the face of environmental change, biology responds — organisms often compensate, adapt and change the nature of their ecologies. But exactly how important is this biological feedback to how ecosystems respond to a warmer world?

My colleagues and I have called for a need to focus on quantifying the importance of what we call the three As — acclimation, adaptation and assembly — on ecosystem-level processes such as carbon flux.

Acclimation is a plastic response by an organism to a change in the environment, whereas adaptation is the end result of natural selection in populations. Assembly is how species come to dominate a local environment and is the result of ecological interactions. We know that all these processes are affected by changes in climate. The end result of the three As is a group of species that live in a given location and control the flow of resources and energy.

These processes operate on differing time scales and have mostly been studied in isolation. However, two fascinating papers (K. Ishikawa et al. New Phytol. 176, 356–364; 2007, and C. Campbell et al. New Phytol. 176, 375–389; 2007) assess the role of both acclimation processes and between-species adaptation in the responses of photosynthesis and respiration to changing temperature. Remarkably, they find that acclimation and adaptative responses seem to compensate for temperature-driven changes in carbon flux.

Putting these two As together with how species assemble in ecological communities will probably reveal generalities in how evolutionary biology and plant-community ecology matters in global change.

Posted by Brendan Maher at 07:29 PM | Permalink | Comments (1) | TrackBacks (0)