Molecular Cell Biology for the 21st Century

Modern biology is rooted in an understanding of the molecules within cells and of the interactions between cells that allow construction of multicellular organisms. The more we learn about the structure, function, and development of different organisms, the more we recognize that all life processes exhibit remarkable similarities. Molecular Cell Biology concentrates on the macromolecules and reactions studied by biochemists, the processes described by cell biologists, and the gene control pathways identified by molecular biologists and geneticists. In this millennium, two gathering forces will reshape molecular cell biology: genomics, the complete DNA sequence of many organisms, and proteomics, a knowledge of all the possible shapes and functions that proteins employ.

All the concepts of molecular cell biology continue to be derived from experiments, and powerful experimental tools that allow the study of living cells and organisms at higher and higher levels of resolution are being developed constantly. In this fourth edition, we address the current state of molecular cell biology and look forward to what further exploration will uncover in the twenty-first century.
New Discoveries, New Methodologies

Since the publication of the third edition of this text in 1995, extraordinary developments have taken place:
-The entire genomes of yeast, a nematode, and many bacterial species have been sequenced (Chapter 7). Now researchers are racing, with corporate and government sponsorship, to sequence all 3 billion base pairs of the human genome, and thus identify the sequence of each of the ~70,000 proteins it encodes, by the year 2001. How do we store and use this new information? A rapidly developing area of computer science, bioinformatics, is devoted to collecting, organizing, and analyzing DNA and protein sequences (Chapter 7).

- The simultaneous expression of thousands of genes can now be analyzed using newly developed DNA - microarray technology, enhancing our understanding of gene control during development and disease states (Chapter 7).-
 Macromolecular synthesis is now understood to require large multiprotein machines. The detailed structure of the ribosome has advanced our knowledge of the steps in peptide bond formation (Chapter 4), and we now understand many of the proteins that participate in and regulate steps of DNA replication (Chapter 12) and messenger RNA syn-thesis (Chapter 10).

Chromosome painting,using fluorescent in situ hybridization, allows each human chromosome in a metaphase spread to be clearly distinguished on the basis of size and color (Chapter 9). This method greatly increases the sensitivity for detecting chromosomal translocations in cancer cells (Chapter 24).

We now understand a great deal about how chromatin structure is modified by histone acetylation to regulate gene expression, and how the RNA polymerase II holoenzyme interacts with activators and co-activators to regulate transcription (Chapter 10).

Significant advances have been made in understanding the processes that regulate transport into and out of the nucleus through nuclear pore complexes, and their interactions with importins, exportins, and the Ran-GTPase (Chapter 11).

The function of many proteins essential for vesicle budding and fusion, and for targeting proteins to specific subcellular organelles is understood in detail, and our understanding of vesicular transport through the Golgi has undergone a major revision (Chapter 17).

New findings about microfilaments and microtubule dynamics and the role of various motor proteins, including myosin V and kinesin-related proteins, give us a better understanding of cell motility and mitosis (Chapters 18 and 19).

We now understand a great deal more about apoptosis (regulated cell death). New discoveries in the molecular mechanisms of cell death inform our understanding of the mechanisms of development; coverage of the pathways relevant to cell death sheds light on cancer and neurological diseases (Chapter 23).

The essential features of intricate cell signaling pathways that start at cell surface receptors and control cell proliferation, growth, and motility have been identified. For example, the structures of G proteins and G-protein complexes have been determined through x-ray crystallography, and are providing important insights into the mech-anisms by which G proteins regulate many aspects of cell function (Chapter 20).

Countless other new developments are incorporated in this completely rewritten, fully updated fourth edition.top link
Streamlined Coverage

With each edition, and with all that is new, the question arises: What should we cut out and what should we cover to provide the most useful text possible to students and professors of this course? We have consulted with professors across the country and worked closely as an author team to streamline our coverage in each chapter and across the book. In streamlin-ing coverage within a chapter we chose, where appropriate, to illustrate key concepts with one key experiment rather than several. In streamlining coverage across the book we have reorganized and combined chapters to reflect the connections we see between and among topics. And we have added more pedagogical aids to help the student succeed in this course.

The four-part structure of the previous edition continues to reflect our broader concept of the organization of this material. Changes in organization and coverage are noted below.

In Part I,Laying the Groundwork, we present the scope of the book in an all-new Chapter 1. We lay the groundwork for understanding the experimental and conceptual basis of Molecular Cell Biology in Chapters. Coverage of membrane structure and cell organization is now presented early in the book (Chapter 5).

In Part II, Nuclear Control of Cellular Activity,we teach students how genes work. We now discuss transcription and RNA processing (Chapters 10 and 11) before DNA replication, repair, and recombination (Chapter 12). We have moved the chapter on the eukaryotic cell cycle to this part because of its close relationship to those on DNA replication and control of gene expression. In our chapter on gene control in development (Chapter 14), we have added a full section on plant development in the model organism Arabidopsis.

In Part III, Building and Fueling the Cell,we focus on the ways in which proteins work together to make a living cell. We have combined coverage of cellular energetics in plant and animal cells into a single chapter to focus attention on the commonalities in these processes: generation of a proton motive force and its utilization in ATP synthesis (Chapter 16). We have combined discussion of organelle biogenesis and protein secretion into a single chapter on protein sorting to emphasize the multiple mechanisms by which proteins are targeted to specific subcellular locations (Chapter 17).

In Part IV,Cell Interactions, we emphasize how cells interact with each other, in normal and abnormal situations. We have consolidated the discussion of cell adhesion molecules and junctions (Chapter 22) and added a new chapter on cell interactions in development (Chapter 23) that includes expanded information on the role of the TGFβ pathway in determining the overall organization of early vertebrate embryos, and also coverage of regulated cell death. We conclude with a completely new chapter on cancer (Chapter 24), which integrates much material presented earlier in the book, on the cell cycle, cell-cell signaling, DNA repair, and interactions of cells with the extracellular matrix. For the first time, we cover immunology in a hot-linked chapter on our Web site to expose students to the original literature, and to gain the flexibility to update coverage of this fast-moving field.top link
Training the Scientists of Tomorrow

We have always believed that it is critical to present to students the experimental basis of our understanding to show them how we know what we know. We hope that this will demonstrate the dynamic nature of science and prepare them not only to engage actively in scientific research and teaching but also to become educated members of a public that increasingly is asked to deal with complex issues such as environmental toxins, genetically modified foods, and human gene technology.

To further this end, we have added a new set of features to this edition: Perspectives for the Future and Perspectives in the Literature. Perspectives for the Future is a brief essay that gives us an opportunity to discuss potential future developments. Perspectives in the Literature is a relatedcritical-thinking question that challenges students to solve a problem working with original research and review articles and resources available on the Web.

Of course, we want to show students not only how we know what we know but why we do what we do. As in previous editions, our coverage of medical topics, biotechnology, and plant biology is integrated throughout. We know that these topics may be of particular interest to your students, so we have highlighted them in context with clear icons.top link
Text, Figures, and Animations Developed Together



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