Paired-up proteins, cells that glow, and gene-counting robots are examples of recent advances that are sure to change our views of how cells function. Cell biology researchers at a recent meeting demonstrated just how far - and fast - the field is expanding into the realm of technology, and pondered how such advances will take shape both in and out of the laboratory.
T-shirts sporting fantastic images of cell substructures and posters urging "Know Thy Cell" lined the display booths at the 38th annual meeting of the American Society for Cell Biology, held December 11 to 16, 1998, in San Francisco. Nearly 10,000 researchers gathered to hear 3,000 presentations on topics from intracellular structure and gene transcription to protein-folding and the biology of parasites. Although the focus of the keynote address was on genetics and human diseases, what clearly stood out were new technologies and investigations in underlying cellular processes, such as how proteins move in and out of the nucleus or how cells divide.
Gerald Crabtree of Stanford University discussed a surprising finding currently being exploited by biotechnology and pharmaceutical companies as well as in academics - that bringing proteins close together can activate proteins to send signals to the cell and alter its fate. Proteins such as receptors that signal a cell to grow or die can be activated merely by forcing them to pair side by side. The evidence for this method of signal transduction (sensing mechanism) has been accumulating over many years, but Crabtree described how he and others have engineered drugs that bring together selected proteins. This means that investigators, and eventually doctors treating their patients, can use this technique to induce a specific cell signal by administering an otherwise inert drug.
Patrick Brown, also of Stanford University, described applications of genome sequencing projects, which researchers worldwide are racing to complete. The DNA of several bacteria, yeast, the nematode Caenorhabditis elegans, and a significant portion of human DNA have been sequenced. Over twenty thousand genes have been catalogued so far. Researchers are trying to determine what to do with this stockpile of genetic information.
Several biotechnology companies and academic laboratories have begun using DNA microassays to answer biological questions with their genetic databases. Information from these kinds of assays will almost certainly change our opinions about how cells work. The unique tool in these assays is the DNA microchip, a thumb-size microscope slide onto which tens of thousands of genes have been spotted. Robots are used to spot the tiny volumes of DNA from racks of stored vials. A single slide can then contain, for example, the entire set of yeast genes in a neat, accessible, 100-by-100-square lattice. The DNA chip can then be used to discern the levels of expression of many genes at once.
For instance, for years people have wanted to know the difference between cancer cells and normal cells. To find this out using a DNA microassay, investigators isolate and color-label the mRNA of each type of cell. mRNA contains the genes that have been transcribed and are currently in use by the cells. Investigators then expose the microchip to each set of genes. Because genes have the ability to self-associate, the chip will show the difference between cancer cells and normal cells as a difference in the red or green label at each spot. A computer can read these results and discern the difference between the two types of cells. As it turns out, thousands of genes are expressed differently in cancer. No wonder cancer is so difficult to understand. In fact, Brown said, almost any new condition a cell experiences leads to hundreds or thousands of differences in the number and amount of genes being used.
Jennifer Lippincott-Schwartz and colleagues at the National Institutes of Health (NIH) have used green fluorescent protein (GFP) to investigate cellular function, with dramatic results. GFP, the substance that causes certain jellyfish to glow, was isolated several years ago. This small protein can be linked by genetic engineering to almost any other protein and allows an investigator to observe proteins in a live cell using a fluorescent microscope. The NIH researchers have been studying how cells process proteins through the Golgi apparatus and the endoplasmic reticulum (ER), structures long known and studied by biologists through static techniques such as electron microscopy or biochemistry. By observing GFP-linked proteins in the Golgi and ER, Lippincott-Schwartz found that these structures are much more dynamic and variable than previously thought. Lippincott-Schwartz's team showed beautiful movies of living cells with glowing substructures demonstrating that cells sort their material through elaborate tubules and networks that move around the cell by energy-dependent "motor molecules." Their data suggests that cells have internal chemical energy states that allow for both physical structure and rapid and diffusive mixing. Simple, orderly pathways for organelle processing, as presented in biology textbooks, will have to be reinterpreted in light of these dynamic observations.
Cell biology is being transformed dramatically by new technologies. Pharmaceutical and biotechnology companies have major roles in many of these developments, and individual researchers can easily be overwhelmed by the
size and dominance of some of these companies. For those of us working
in small academic labs we can take comfort that these new ideas come from individuals and that these ideas, whether implemented by large companies or small academic labs, are making tremendous progress.
John Murray is a postdoc in the laboratory of Allan Wokoff
at the Albert Einstein College of Medicine in New York City.
Send us your comments and ideas for future articles.
Golgi Membrane Dynamics - fascinating movies of intracellular movement made possible by the use of the green fluorescent protein. From the July 1998 issue of Molecular Biology of the Cell. Other "video essays" on the use of microscopy of living tissues are available from this site. Requires paid subscription for access.
Dictionary of Cell Biology - online dictionary of cell biology. This is a great idea - a clickable map of a cell leads to easily understood and cross-referenced definitions of terms frequently encountered in modern biology literature.
Gerald Crabtree of Stanford University discussed a surprising finding currently being exploited by biotechnology and pharmaceutical companies as well as in academics - that bringing proteins close together can activate proteins to send signals to the cell and alter its fate. Proteins such as receptors that signal a cell to grow or die can be activated merely by forcing them to pair side by side. The evidence for this method of signal transduction (sensing mechanism) has been accumulating over many years, but Crabtree described how he and others have engineered drugs that bring together selected proteins. This means that investigators, and eventually doctors treating their patients, can use this technique to induce a specific cell signal by administering an otherwise inert drug.
Several biotechnology companies and academic laboratories have begun using DNA microassays to answer biological questions with their genetic databases. Information from these kinds of assays will almost certainly change our opinions about how cells work. The unique tool in these assays is the DNA microchip, a thumb-size microscope slide onto which tens of thousands of genes have been spotted. Robots are used to spot the tiny volumes of DNA from racks of stored vials. A single slide can then contain, for example, the entire set of yeast genes in a neat, accessible, 100-by-100-square lattice. The DNA chip can then be used to discern the levels of expression of many genes at once.
Jennifer Lippincott-Schwartz and colleagues at the 
