What can surface chemistry do for cell biology?

Recent research has enhanced the development of substrates that serve as models of extracellular matrix and their use in studies of cell adhesion and migration. Advances include the development of methods to prepare substrates having ligands immobilized in controlled densities and patterns, and recent work that is developing dynamic substrates which can modulate, in real-time, the activities of ligands. These technologies are providing new opportunities for studies of cell-extracellular-matrix interactions.     

What can biological barcoding do for marine biology?

The idea of using nucleotide sequences as barcodes for species identification has stirred up debates in the community of taxonomists and systematists. We argue that barcodes are potentially extremely useful tools for taxonomy for several reasons. Barcodes may, for example, help to identify cryptic and polymorphic species and give means to associate life history stages of unknown identity. Barcode systems would thus be particularly helpful in cases when morphology is ambiguous or uninformative and would provide tools for higher taxonomic resolution of disparate life forms. Comparative analysis of short DNA sequences may also represent heuristic access cards to a deeper understanding of evolutionary relationships between organisms. However, barcodes are the “essence” of species identities no more than taxonomic holotypes are “the species”. It makes no sense to think that morphology and other biological information about organisms can be made obsolete by barcode systems. The biological significance of matching or diverging nucleotide sequences will still have to be the subject of taxonomic decisions that must be open for scrutiny. It is imperative, therefore, that barcodes are associated with specimen vouchers.     

What can GPI do for you?

Various functions for glycosylphosphatidylinositol (GPI) protein anchors have been described in mammalian and protozoan systems. These data suggest that some functions are common to higher and lower eukaryotes, whereas others may represent adaptations that are specifically advantageous to either unicellular or metazoan organisms. In this article, Mike Ferguson discusses the current theories of GPI function that have relevance to protozoan parasites and their mammalian hosts.     

What can spores do for us?

Many organisms have the ability to form spores, a remarkable phase in their life cycles. Compared with vegetative cells, spores have several advantages (e.g. resistance to toxic compounds, temperature, desiccation and radiation) making them well suited to various applications. The applications of spores that first spring to mind are bio-warfare and the related, but more positive, field of biological control. Although they are often considered metabolically inert, spores can also be used as biocatalysts. Other uses for spores are found in the fields of probiotics, tumour detection and treatment, biosensing and in the "war against drugs".     

What can epigenomics do for you?

Genome-wide 5-hydroxymethylome analysis of a rodent hepatocarcinogen model reveals that 5-hydroxymethylcytosine-dependent active DNA demethylation may be functionally important in the early stages of carcinogenesis. See research article http://genomebiology.com/2012/13/10/R93     

What can feruloyl esterases do for us?

The role of feruloyl esterases in plant wall development, in gut health, and in the breakdown of plant biomass for the production of bioactive phytochemicals and biofuel is covered in this review. These enzymes have potential roles in stomatal cell function and the phenolic substitutions and cross-linkages between plant cell wall components. As more plant genomes are sequenced, the role of ferulic acid and feruloyl esterases in planta may be better understood. In human and ruminal digestion, these enzymes are important to de-esterify dietary fibre, releasing hydroxycinnamates and derivatives which have been shown to have positive health effects, such as antioxidant, anti-inflammatory and anti-microbial activities. They are also involved in colonic fermentation where their extracellular and intracellular activities in the microbiota improve the breakdown of polysaccharides and increase microbial production of short chain fatty acids. Their specificity can also be employed to synthesize bioactive compounds for cosmetic and health applications. The enzymatic disassembly of cereal straws is greatly enhanced when feruloyl esterase activity is present, although the substrate specificity of the esterase appears to have some bearing on its optimal application. The involvement of feruloyl esterases in the improved enzymatic and microbial saccharification of cereal-derived material demonstrates a high importance for these enzymes in animal feed preparation and bioalcohol production.     

What can AlphaFold do for antimicrobial amyloids?

Amyloids, protein, and peptide assemblies in various organisms are crucial in physiological and pathological processes. Their intricate structures, however, present significant challenges, limiting our understanding of their functions, regulatory mechanisms, and potential applications in biomedicine and technology. This study evaluated the AlphaFold2 ColabFold method's structure predictions for antimicrobial amyloids, using eight antimicrobial peptides (AMPs), including those with experimentally determined structures and AMPs known for their distinct amyloidogenic morphological features. Additionally, two well-known human amyloids, amyloid-β and islet amyloid polypeptide, were included in the analysis due to their disease relevance, short sequences, and antimicrobial properties. Amyloids typically exhibit tightly mated β-strand sheets forming a cross-β configuration. However, certain amphipathic α-helical subunits can also form amyloid fibrils adopting a cross-α structure. Some AMPs in the study exhibited a combination of cross-α and cross-β amyloid fibrils, adding complexity to structure prediction. The results showed that the AlphaFold2 ColabFold models favored α-helical structures in the tested amyloids, successfully predicting the presence of α-helical mated sheets and a hydrophobic core resembling the cross-α configuration. This implies that the AI-based algorithms prefer assemblies of the monomeric state, which was frequently predicted as helical, or capture an α-helical membrane-active form of toxic peptides, which is triggered upon interaction with lipid membranes.     

What can light scattering spectroscopy do for membrane-active peptide studies?

Highly charged peptides are important components of the immune system and belong to an important family of antibiotics. Although their therapeutic activity is known, most of the molecular level mechanisms are controversial. A wide variety of different approaches are usually applied to understand their mechanisms, but light scattering techniques are frequently overlooked. Yet, light scattering is a noninvasive technique that allows insights both on the peptide mechanism of action as well as on the development of new antibiotics. Dynamic light scattering (DLS) and static light scattering (SLS) are used to measure the aggregation process of lipid vesicles upon addition of peptides and molecular properties (shape, molecular weight). The high charge of these peptides allows electrostatic attraction toward charged lipid vesicles, which is studied by zeta potential (zeta-potential) measurements.     

What can we do about osteoarthritis?

Osteoarthritis is complex in genetics, pathogenesis, monitoring and treatment. Current treatment of osteoarthritis does not influence progression. Much could be gained by more effective 'low-tech-low-cost' treatment. However, many patients have rapidly progressive disease, multiple joint involvement, and severe disease. We need to clarify the genetics of osteoarthritis, identify those at risk for progression and severe disease, and identify molecular processes critical for joint survival and failure. Will saving the cartilage improve patient pain and function? Effective outcome measures are needed to accelerate testing of new treatments. Further improvement is needed in joint implant technology to decrease costs, wear and loosening.     

What can genome-scale metabolic network reconstructions do for prokaryotic systematics?

It has recently been proposed that in addition to Nomenclature, Classification and Identification, Comprehending Microbial Diversity may be considered as the fourth tenet of microbial systematics [Staley JT (2010) The Bulletin of BISMiS, 1(1): 1–5]. As this fourth goal implies a fundamental understanding of microbial speciation, this perspective article argues that translation of bacterial genome sequences into metabolic features may contribute to the development of modern polyphasic taxonomic approaches. Genome-scale metabolic network reconstructions (GSMRs), which are the result of computationally predicted and experimentally confirmed stoichiometric matrices incorporating all enzyme and metabolite components encoded by a genome sequence, provide a platform that can illustrate bacterial speciation. As the topology and the composition of GSMRs are expected to be the result of adaptive evolution, the features of these networks may provide the prokaryotic taxonomist with novel tools for reaching the fourth tenet of microbial systematics. Through selected examples from the Actinobacteria, which have been inferred from GSMRs and experimentally confirmed after phenotypic characterisation, it will be shown that this level of information can be incorporated into modern polyphasic taxonomic approaches. In conclusion, three specific examples are illustrated to show how GSMRs will revolutionize prokaryotic systematics, as has previously occurred in many other fields of microbiology.     

What can neurons do for their brain? Communicate selectivity with bursts

Neurons deep in cortex interact with the environment extremely indirectly; the spikes they receive and produce are pre- and post-processed by millions of other neurons. This paper proposes two information-theoretic constraints guiding the production of spikes, that help ensure bursting activity deep in cortex relates meaningfully to events in the environment. First, neurons should emphasize selective responses with bursts. Second, neurons should propagate selective inputs by burst-firing in response to them. We show the constraints are necessary for bursts to dominate information-transfer within cortex, thereby providing a substrate allowing neurons to distribute credit amongst themselves. Finally, since synaptic plasticity degrades the ability of neurons to burst selectively, we argue that homeostatic regulation of synaptic weights is necessary, and that it is best performed offline during sleep.     

What can myosin VI do in cells?

The recently solved structure of the myosin VI motor demonstrates that the unique insert at the end of the motor is responsible for the reversal of the normal myosin directionality. A second class-specific insert near the nucleotide-binding pocket contributes to myosin VI's unique kinetic tuning, allowing it to function either as an actin-based transporter or as an anchoring protein. Recent biochemical and biophysical studies have shown that the native molecule can form dimers upon clustering, and cell biological studies have demonstrated that it clearly does play both transport and anchoring roles in cells. These mechanistic insights allow us to speculate on how unusual aspects of myosin VI structure and function allow it to fill unique niches in cells.     

Ultrastructure in cell biology: do we still need it?

John Heuser is being honored in this special issue for his enormous contributions to cell biology using morphological approaches. Foremost in this context is his ability to use light and electron microscopy to visualize structures and processes such that the information has both scientific and artistic value. The beauty of his images helps to focus the observer more intensely on the scientific messages, which have been numerous and important. His recent studies of living cells using state-of-the-art light and video microscopy fits into a general pattern of a huge explosion in the application of these methods worldwide that is revolutionizing cell biology. However, whereas John Heuser continues to use light microscopy (LM) for a low-resolution global and dynamical overview he then moves on to the electron microscopy (EM) level to see the details; in this he is--unfortunately--in a minority; and EM is an approach that a majority of today's cell biologists never use. The continued drop in EM usage has already been articulated in recent reviews. Here, I suggest that an additional problem for EM in cell biology, in its continued crises, is the declining number of scientists who can confidently interpret the--admittedly--complex information in most electron micrographs of cells. A major re-education is needed, or cell biology as a discipline will have a real problem in the 21st century.