A structural biologist's view of the oestrogen receptor

Here we review the results that have emerged from our structural studies on the oestrogen receptor ligand-binding domain (ER-LBD). The effects of agonists and antagonists on the structure of ER- and ERβ-LBDs are examined. In addition, the findings from structural studies of ER-LBD in complex with peptide fragments corresponding to the NR-box II and III modules of the p160 coactivator TIF2 are discussed in the context of the assembly of ER:coactivator complexes. Together these studies have broadened our understanding of ER function by providing a unique insight into ER's ligand specificity, it's ability to interact with coactivators and the structural changes that underlie receptor agonism and antagonism.     

Molecular biologist's guide to proteomics.

The emergence of proteomics, the large-scale analysis of proteins, has been inspired by the realization that the final product of a gene is inherently more complex and closer to function than the gene itself. Shortfalls in the ability of bioinformatics to predict both the existence and function of genes have also illustrated the need for protein analysis. Moreover, only through the study of proteins can posttranslational modifications be determined, which can profoundly affect protein function. Proteomics has been enabled by the accumulation of both DNA and protein sequence databases, improvements in mass spectrometry, and the development of computer algorithms for database searching. In this review, we describe why proteomics is important, how it is conducted, and how it can be applied to complement other existing technologies. We conclude that currently, the most practical application of proteomics is the analysis of target proteins as opposed to entire proteomes. This type of proteomics, referred to as functional proteomics, is always driven by a specific biological question. In this way, protein identification and characterization has a meaningful outcome. We discuss some of the advantages of a functional proteomics approach and provide examples of how different methodologies can be utilized to address a wide variety of biological problems.     

The Leeuwenhoek lecture, 1985. A molecular biologist's view of viral hepatitis

Three forms of viral hepatitis can be distinguished serologically. Hepatitis A virus is a picornavirus, which is being studied increasingly after its propagation in cell cultures. The B virus (HBV) is the prototype of a family now termed hepadna viruses and is by far the best understood. The third, by exclusion, is non-A non-B, about which little else is known. Molecular cloning methods enable copies of viral genes to be propagated and analysed quite readily and provide the means for isolation and expression of individual genes in microbial and animal cells. Determination of the nucleotide sequences of HBV DNA revealed its genetic organization and so guided studies of the mechanism of gene expression both in infected animals and cultures of transformed cells. Replication of the viral genome has also been studied in natural infections, particularly with duck HBV, but also with the human virus. Expression of HBV genes in microbial cells is valuable as a source of antigens for diagnostic reagents and vaccine preparations, but has also been of consequence for the identification of viral gene products not previously recognized and which are of considerable current interest. The methods and materials now available provide additional opportunities for inquiring into the course of viral infection, replication of the virus and, for HBV, the possible role in the development of hepatomas of integration of the viral genome into the host chromosome.     

Get ready to GO! A biologist's guide to the Gene Ontology

The Gene Ontology (GO) project provides a controlled vocabulary to facilitate high-quality functional gene annotation for all species. Genes in biological databases are linked to GO terms, allowing biologists to ask questions about gene function in a manner independent of species. This tutorial provides an introduction for biologists to the GO resources and covers three of the most common methods of querying GO: by individual gene, by gene function and by using a list of genes. [For the sake of brevity, the term 'gene' is used throughout this paper to refer to genes and their products (proteins and RNAs). GO annotations are always based on the characteristics of gene products, even though it may be the gene that is cited in the annotation.].     

Representing ontogeny through ontology: A developmental biologist's guide to the gene ontology

Developmental biology, like many other areas of biology, has undergone a dramatic shift in the perspective from which developmental processes are viewed. Instead of focusing on the actions of a handful of genes or functional RNAs, we now consider the interactions of large functional gene networks and study how these complex systems orchestrate the unfolding of an organism, from gametes to adult. Developmental biologists are beginning to realize that understanding ontogeny on this scale requires the utilization of computational methods to capture, store and represent the knowledge we have about the underlying processes. Here we review the use of the Gene Ontology (GO) to study developmental biology. We describe the organization and structure of the GO and illustrate some of the ways we use it to capture the current understanding of many common developmental processes. We also discuss ways in which gene product annotations using the GO have been used to ask and answer developmental questions in a variety of model developmental systems. We provide suggestions as to how the GO might be used in more powerful ways to address questions about development. Our goal is to provide developmental biologists with enough background about the GO that they can begin to think about how they might use the ontology efficiently and in the most powerful ways possible. Mol. Reprod. Dev. 77: 314–329, 2010. © 2009 Wiley‐Liss, Inc.     

Microscopy in 3D: a biologist's toolbox

The power of fluorescence microscopy to study cellular structures and macromolecular complexes spans a wide range of size scales, from studies of cell behavior and function in physiological 3D environments to understanding the molecular architecture of organelles. At each length scale, the challenge in 3D imaging is to extract the most spatial and temporal resolution possible while limiting photodamage/bleaching to living cells. Several advances in 3D fluorescence microscopy now offer higher resolution, improved speed, and reduced photobleaching relative to traditional point-scanning microscopy methods. We discuss a few specific microscopy modalities that we believe will be particularly advantageous in imaging cells and subcellular structures in physiologically relevant 3D environments.     

Harry Potter and the structural biologist's (Key)stone

A report on the first European Keystone symposium 'Multi-protein complexes involved in cell regulation', Cambridge, UK, 18-23 August 2006.     

Life and death: a biologist's view.

The strict link between life and death of an organism should be discussed and compared to the life cycles of molecules and cells that allow the organism's development and survival. Indeed, a brief consideration of the main features of biological functions reveals that they occur at widely different levels of organization, ranging from molecules to species and ecological systems, and occupying widely different spatio-temporal domains. Biological functions are characterized by the integrated motion of their constitutive parts, and operate in cyclic fashions that comprise on and off phases. The birth and death of molecules, cells, organisms or species represent a special class of cycling functions that support the life cycles of the entities that include them. Under this perspective, the life cycles of past, present and future human beings may be viewed as necessary support to the longer lasting and more widely spreading life cycles of families, nations, and civilizations. If due consideration is given to our deep mental nature, one may cherish the conclusion that past, present and future human beings may be all supporting the life cycle of a superior mental entity that includes us in the same way we include our own cellular and molecular components.     

Harry Potter and the structural biologist's (Key)stone

A report on the first European Keystone symposium 'Multi-protein complexes involved in cell regulation', Cambridge, UK, 18-23 August 2006.     

A biologist's guide to de novo genome assembly using next-generation sequence data: A test with fungal genomes

We offer a guide to de novo genome assembly¹ using sequence data generated by the Illumina platform for biologists working with fungi or other organisms whose genomes are less than 100 Mb in size. The guide requires no familiarity with sequencing assembly technology or associated computer programs. It defines commonly used terms in genome sequencing and assembly; provides examples of assembling short-read genome sequence data for four strains of the fungus Grosmannia clavigera using four assembly programs; gives examples of protocols and software; and presents a commented flowchart that extends from DNA preparation for submission to a sequencing center, through to processing and assembly of the raw sequence reads using freely available operating systems and software.     

The biology of ethics or the ethics of biology? The biologist's quest for meaning

The biologist's involvement in value issues concerning the methodology of biological sciences, in establishing the biological basis of ethics and in creating a value system based on biological knowledge is examined. It is proposed that the roots of this involvement are in the conflict of the knowledge-ethic with the established system of values and in the need for metaphysical explanation.This essay is dedicated to the memory of I. Michael Lerner, formerly Professor of Genetics University of California, Berkeley.