Methods for Manipulating Synaptic Plasticity

Drosophila Neurobiology: A Laboratory Manual is “an unparalleled resource for the fly neurobiology novice and aficionado” according to a recent review in The Quarterly Review of Biology. Konrad Zinsmaier, the reviewer, described it as an “almost ‘foolproof’ manual” in which each chapter is “well organized, and features a concise introduction, critical references, and detailed experimental protocols.”

One such article, which outlines methods and tools for studying synaptic plasticity in Drosophila, is featured in this month’s issue of Cold Spring Harbor Protocols. The Drosophila larval neuromuscular junction (NMJ) is a well-established model for studying synaptic function; both the motor neurons and the target muscle cells can be directly manipulated at the cellular and molecular levels. In the article, Haig Keshishian provides an overview of experimental genetic methods to manipulate these synaptic connections – including the use of mutated or reengineered ion channels. He also discusses environmental and rearing conditions that phenocopy the genetic approaches that affect synaptic function.

The article is freely accessible from Cold Spring Harbor Protocols here. For more information about Drosophila Neurobiology: A Laboratory Manual, click here.

 

“A Fascinating Adventure in Biomedical Research”

Alzheimer disease insidiously attacks the brain and deprives people of their most human qualities, leading to memory loss, behavior changes, and ultimately, death. An essay in this month’s issue of Cold Spring Harbor Perspectives in Medicine provides an excellent overview of modern Alzheimer research, its origins and development, scope, driving forces, and key questions, as well as competing ideas and findings within the field. It was written by Dennis Selkoe, Eckhard Mandelkow, and David Holtzman, editors of our recent book The Biology of Alzheimer Disease.

In the essay, Selkoe and colleagues outline key developments that followed the first description of the disease by Alois Alzheimer in 1907.  They explain how the discoveries of tau and amyloid β-protein precursor in the late 1980s and early 1990s brought Alzheimer research into sync with basic research in molecular genetics and protein chemistry.  Furthermore, the recognition of Alzheimer disease as a common disorder – currently estimated to affect 20-25 million people worldwide – has helped define it as an urgent problem in biomedical research.

But beyond that, Selkoe and colleagues describe how tackling a complicated disease – and one that affects the most human qualities of memory, reasoning, language, and emotion – can be intellectually rewarding. “The complexity of the problem and the diverse ways in which one might think about approaching it make for a fascinating adventure in biomedical research,” they write.

For more on Alzheimer research – including discussion of competing ideas between “BAPtists” and “TAUists” – read the complete essay here.

 

New Book on Angiogenesis

The growth and survival of tumors depends on angiogenesis, the process by which new blood vessels are formed from preexisting vessels.  Similar processes are required for proper embryonic development, patterning of the vascular system, and wound healing.  Our new book Angiogenesis: Biology and Pathology reviews the mechanisms of angiogenesis that operate in normal and disease states.

In 30 chapters, contributors review the biology of endothelial cells, describing the specific roles of tip and stalk cells in vessel sprouting and formation. They discuss key angiogenic regulators (e.g., VEGF), as well as antiangiogenic agents including microRNAs, thrombospondins, and semaphorins.  Therapeutic approaches that target pathological angiogenesis, such as the ongoing clinical trials of anti-VEGF drugs, are also covered.

“It is hoped that the vast amount of basic knowledge about angiogenesis that has been acquired over the last four decades and reported in this volume will result in improved therapies for angiogenesis-dependent disease,” write the editors, Michael Klagsbrun and Patricia D’Amore.

Angiogenesis: Biology and Pathology is a vital reference for developmental and cancer biologists, as well as anyone seeking to understand the biology and pathology of the vascular system.  For more details on the book, click here.

 

New Book on HIV Research

The worldwide AIDS epidemic makes research on HIV, the disease processes it induces, and potential HIV therapies among the most critical in biomedical science. Our new book HIV: From Biology to Prevention and Treatment reviews the current state of HIV research.

“There was once a time when a scholar could expect to read all the literature in their field, but for HIV this task is now impossible” write the editors, Frederic Bushman, Gary Nabel, and Ronald Swanstrom. “In 2010, fully 13,188 papers were published on HIV. Given this scale, it is evident that comprehensive reviews of HIV research areas are critical for understanding AIDS.”

HIV: From Biology to Prevention and Treatment contains 29 chapters, in which expert contributors explore the origins and evolution of HIV, the HIV replication cycle, host-virus interactions, host immune responses, and HIV transmission.  Vaccines, cell and gene therapies, antiretroviral drugs, microbicides, and behavioral strategies for the treatment and prevention of HIV are also explored.  For more details on the book, click here.

 

Tracking Worm Behavior

The colorful scribbles on this month’s cover of Cold Spring Harbor Protocols are tracks from one wild-type worm as it crawls through food on an agar dish.  Such images can reveal movement and behavioral patterns in C. elegans. (If you look closely, you can see evidence of pirouettes and foraging behavior.)

Initial methods to analyze behavioral phenotypes in C. elegans relied on human observation, and were therefore subjective and imprecise. Terms like “sluggish” or “loopy” were used to describe the uncoordinated activity of some mutants. And the procedures were often time-consuming, as the observer was required to monitor worm behavior in real time.

But, as described by Bill Schafer and colleagues in the current issue of Cold Spring Harbor Protocols, automated microscopy and image analysis systems for recording and analyzing worm behavior are much more robust.  They allow for precise quantitative definitions of behavioral phenotypes, and permit the analysis of behaviors that occur over long time periods or are difficult to detect by eye.

In the issue, Schafer and colleagues provide protocols for preparing media and worms for automated tracking and image analysis, describe high-throughput worm behavior analysis using Multiworm Tracker, and offer strategies for obtaining uniform illumination during worm tracking.  They also compare and contrast single- and multi-worm tracking approaches, and describe how comparisons of wild-type and genetically modified worms can be used to functionally dissect the molecular mechanisms behind specific behaviors.

 

New Book on Alzheimer Disease Biology

Understanding the complex changes that occur during Alzheimer disease—including the accumulation of amyloid plaques and neurofibrillary tangles in the brain—is critical for the development of successful therapeutic approaches.  Our newest book, The Biology of Alzheimer Disease, provides a current and comprehensive review of the biological basis of Alzheimer disease (AD).

The editors, Dennis Selkoe, Eckhard Mandelkow, and David Holtzman, chose leading researchers in Alzheimer biology to contribute chapters on topics in which they have deep expertise. The 25 chapters include contributions covering all aspects of Alzheimer disease, from our current molecular understanding of it to therapeutic agents that could be used to treat and prevent it.

Additionally, the first and last chapters provide the editors’ perspectives on the disease, its challenges and prospects for developing effective treatments. “[We] have tried to step back from the wealth of details and convey a sense of what has motivated the global quest to understand the biology of AD, how sometimes competing concepts and lines of inquiry have proceeded, and, most importantly, where we believe this scientifically rich and therapeutically promising field is headed,” they write.

The book is a vital reference for neurobiologists, cell biologists, pathologists, and other scientists pursuing the biological basis of Alzheimer disease, as well as investigators, clinicians, and students interested in its pathogenesis, treatment, and prevention.  For more details, click here.

 

RNA: Life’s Indispensable Molecule is Reviewed in Cell

James Darnell’s recent book is given a wonderful review in the current issue of Cell. “Darnell has succeeded in writing an appealing and cogent account of the rise of RNA molecular biology and its continued centrality in research today,” write the reviewers Kristian Baker and Tim Nilsen.

This is an “excellent book” that describes key historical experiments in a “straightforward and enjoyable way,” say Baker and Nilsen. The “informative figures” and “up-to-date referencing” are a “significant plus.” They conclude that it “should be required reading for graduate students and more senior investigators alike.”

 

New Book on Protein Homeostasis

Cellular health depends on the proper expression, folding, and degradation of thousands of proteins. Protein Homeostasis, recently released by CSHL Press, covers the mechanisms by which cells ensure efficient functioning of the proteome, and the diseases that result when these processes go awry.

“Protein Homeostasis addresses the remarkable story of the life of proteins,” write the editors, Richard Morimoto, Dennis Selkoe, and Jeffrey Kelly. The contributors examine the physical biochemistry of protein folding; the cellular compartments involved in protein quality control; the various chaperones, translocation machineries, proteasomes, and autophagic activities; and the role of proteostasis in aging and disease.

Protein Homeostasis is invaluable for molecular and cellular biologists, as well as medical scientists wishing to understand the pathological consequences of and potential therapies for protein homeostasis deficiencies in common human diseases. For details on the book, click here.

 

Crick at the Foundation

Robert Olby’s widely praised biography of Francis Crick was one of the items in a time capsule that was recently buried in the foundation of The Francis Crick Institute, a £660,000,000 biomedical research center under construction in Central London that is scheduled to open in 2015.

The brass capsule, buried by Crick’s daughter Gabrielle, also included letters from scientists, photographs, artwork, and other memorabilia representing Crick, the Institute, its ambitions and locale.  “In this time capsule, we are making clear our aspirations for the Institute to future generations,” said Sir Paul Nurse, the Director and Chief Executive of the Institute, during the ceremony.

Most of Crick’s long life in science was spent on two fundamental problems in biology: how molecules create life and how the brain creates consciousness. To both, he brought his initial training in physics, a discipline judged to have achieved remarkable progress in the 20^th century, endowing him confidence (or immodesty, in the eyes of at least one observer) that problems in biology were similarly susceptible to solution. Echoing Crick’s optimism, Sir Paul said that by bringing together many of the world’s best scientists and clinicians, the Institute aims to improve lives and help deliver the innovations that will bring long-lasting benefits to the economy and people’s health.

Between 1947 and 1977 in Cambridge, Crick became molecular biology’s leading theorist, laying foundations for the elucidation of the triplet code, an understanding of the flow of genetic information, and the machinery for synthesis of proteins.  His subsequent years in California until his death in 2004 were devoted to studies of consciousness.  Although the problem proved unyielding and this period of his life failed to provide the scientific success he hoped for, Crick lived long enough to see the emergence of a new generation of scientists with the confidence, and the research tools, to ask questions about the nature of mind that had previously been the terrain of philosophy and the humanities.  He would have greatly enjoyed – and would no doubt have elegantly contributed to – the recent sparring on the relationship between neuroscience and the humanities in the opinion pages of The New York Times. In those articles, and several of the well-informed comments that followed, Crick’s presence at the foundation can be seen once again.

 

New Book on the Extracellular Matrix

The extracellular matrix (ECM) plays a role in the function of virtually all cells, regulating cellular morphology, adhesion, cell migration, cell proliferation, and apoptosis. Extracellular Matrix Biology, a new book from CSHL Press, covers ECM composition and function, as well as its roles in development, physiology, and pathology.

“We have endeavored to illustrate the manifold aspects of ECM biology,” write the editors Richard Hynes and Kenneth Yamada. Contributors discuss the various ECM proteins and proteoglycans, ECM receptors such as integrins, and the signaling pathways that mediate the effects of the ECM on cells. They also describe ECM functions in specific biological contexts, including angiogenesis, hemostasis, and thrombosis.

“We hope that this collection of reviews by experts in the field will serve to promote research leading to discoveries and applications based on improved understanding of the ECM,” write Hynes and Yamada. Extracellular Matrix Biology is an indispensable reference for cell biologists and all those interested in exploring the myriad functions of the ECM.  For more details on the book, click here.