Bigger, Faster, Better? Rhetorics and Practices of Large-Scale Research in Contemporary Bioscience

publication-status: Publishedtypes: ArticleEditorial for Special Issu

State-of-the-art microscopy to understand islets of Langerhans:what to expect next?

The discovery of Langerhans and microscopic description of islets in the pancreas were crucial steps in the discovery of insulin. Over the past 150 years, many discoveries in islet biology and type 1 diabetes have been made using powerful microscopic techniques. In the past decade, combination of new probes, animal and tissue models, application of new biosensors and automation of light and electron microscopic methods and other (sub)cellular imaging modalities have proven their potential in understanding the beta cell under (patho)physiological conditions. The imaging evolution, from fluorescent jellyfish to real-time intravital functional imaging, the revolution in automation and data handling and the increased resolving power of analytical imaging techniques are now converging. Here, we review innovative approaches that address islet biology from new angles by studying cells and molecules at high spatiotemporal resolution and in live models. Broad implementation of these cellular imaging techniques will shed new light on cause/consequence of (mal)function in islets of Langerhans in the years to come

The TOR Signaling Pathway in Spatial and Temporal Control of Cell Size and Growth

Cell size is amenable by genetic and environmental factors. The highly conserved nutrient-responsive Target of Rapamycin (TOR) signaling pathway regulates cellular metabolic status and growth in response to numerous inputs. Timing and duration of TOR pathway activity is pivotal for both cell mass built up as well as cell cycle progression and is controlled and fine-tuned by the abundance and quality of nutrients, hormonal signals, growth factors, stress, and oxygen. TOR kinases function within two functionally and structurally discrete multiprotein complexes, TORC1 and TORC2, that are implicated in temporal and spatial control of cell size and growth respectively; however, recent data indicate that such functional distinctions are much more complex. Here, we briefly review roles of the two complexes in cellular growth and cytoarchitecture in various experimental model systems

Sphingolipid accumulation causes mitochondrial dysregulation and cell death

Sphingolipids are structural components of cell membranes that have signaling roles to regulate many activities, including mitochondrial function and cell death. Sphingolipid metabolism is integrated with numerous metabolic networks, and dysregulated sphingolipid metabolism is associated with disease. Here, we describe a monogenic yeast model for sphingolipid accumulation. A csg2Δ mutant cannot readily metabolize and accumulates the complex sphingolipid inositol phosphorylceramide (IPC). In these cells, aberrant activation of Ras GTPase is IPC-dependent, and accompanied by increased mitochondrial reactive oxygen species (ROS) and reduced mitochondrial mass. Survival or death of csg2Δ cells depends on nutritional status. Abnormal Ras activation in csg2Δ cells is associated with impaired Snf1/AMPK protein kinase, a key regulator of energy homeostasis. csg2Δ cells are rescued from ROS production and death by overexpression of mitochondrial catalase Cta1, abrogation of Ras hyperactivity or genetic activation of Snf1/AMPK. These results suggest that sphingolipid dysregulation compromises metabolic integrity via Ras and Snf1/AMPK pathways