Issue | March 2004 | March 2004 | The Scientist Magazine®

Feature

Investigating Molecular Motors Step by Step

Jeffrey Perkel | Mar 14, 2004 | 10+ min read

Thom Graves MediaThe audience, several hundred biophysicists strong, was not expecting a James Brown impersonation. But there he was: Physiologist Yale Goldman, keynote speaker on motility at the Biophysical Society's annual meeting, doing his "asymmetric hand-over-hand motility dance with a limp" to tinny strains of "Papa's Got a Brand New Bag." And while Goldman, who eschewed Brown's trademark, over-the-top couture for understated, Ivy League-issue khakis and blue blazer, won't star on MTV any

Editorial

The Globalization of Science: Reality Confronts an Ideal

To survive in the world we have transformed, we must learn to think in a new way. As never before, the future of each depends on the good of all.1- Statement by 100 Nobel laureatesGlobalization has multiple personas; one of the more benevolent extols a world of mutual cooperation and interdependence. In recent weeks, much ink has been spilled over the contribution that science and technology can make to this idyll of global security and prosperity. Most notable of these was the debut of the Inte

Opinion

Reducing Risks, Maximizing Impact with Cancer Biomarkers

Brad FitzpatrickBiomarkers measure drug-induced changes in a patient's blood or tissue. Such changes can confirm drug activity and thereby help select patients more likely to respond to treatment. These biochemicals are revolutionizing cancer drug development.It's a revolution sorely needed. A recent Nature Medicine story described 2003 as filled "with hype and hope for cancer drugs ... [The year] saw no shortage of cancer headlines ... But recent successes have not been unequivocal, and emphasi

Letter

On Abandonware

Thank you very much for writing this story.1 I used a first version of a molecular biology software system in 1978. It came on a tape and I used it on a remote Cyber70 mainframe computer through a teletype. Over the years, this package got more complicated. The user interface was maybe OK for computer gurus, but not for my lab technicians or my summer students.Software developers at universities and research institutes create brilliant alpha versions and algorithms, but never move beyond this st

Morning Mitoses

Your story about Dr. Kay1 and plant rhythms reminded me of a story my botany professor told us about his MS research. The year was 1950.He was looking for growth periods in tomatoes and decided that he would look for mitotic figures in the hair root tips, where they should be abundant. He spent many hours during the afternoon, evening, then morning but found next to nothing. So he decided to check every hour on the hour starting at midnight. Between 3:00 and 4:00 am the root tips were loaded wit

A New Cold War?

For those of you who missed the Cold War and its 40 years of denunciations, mistrust, and calumny, it is difficult to understand what life was like in science during those times. Not the major affronts like the persecution of Sakharov and the ascendancy of Lysenko. It was the little things, like sending research letters to friends or wondering how to send journal subscriptions with any hope of their arrival, or the care package of pilfered Eppendorf tips and microtiter plates sent with travelers

Another View on AIDS

Why in your Editorial on AIDS1 do you dismiss out of hand all the counter evidence that HIV causes AIDS? The minority of dissenters are not stupid, but bona fide scientists, some of whom are retro-virus experts. You should listen to their viewpoint instead of arrogantly assuming that they are wrong. History may yet make fools of you!Dr. M. WainwrightDepartment of Molecular Biology and Biotechnology University of Sheffield, UK chris@chriswainwright.freeserve.co.uk

Disclosing Monies Spent

"The pace, direction, and application of scientific research are largely determined by the availability of money."1 I agree so far, but what the author forgets is that an even more difficult commodity is time. It does not matter how much money we have for research if we have no time left. Time is my most valuable resource, and I find myself spending more time on ridiculous requests for information like the one Dr. Potts suggests. ... He could have spent his $500 to $1000 in a much better way tha

5-Prime

A Talk on the Motor Side

1. What is a molecular motor?Tom Sephton, http://www.funhousefilms.comIt's any protein that uses chemical energy, specifically ATP hydrolysis, to produce physical force.2. How many types of motors are there?Proteins that transport molecules and vesicles along the cytoskeleton; enzymes involved in DNA strand separation and replication, such as helicases, gyrases, and topoisomerases; and ATPases that move ions and large organic molecules across membrances are all motor proteins. Their genes have t

Snapshot

Five-year relative survival rates of pancreatic, female breast, and small-cell lung and bronchus cancers

The relative survival rate represents the probability of a patient living for another five years, as compared to a random person of the same age, race, and sex.See http://seer.cancer.gov/csr/1975_2000/results_merged/topic_survival.pdf for more information.- Christine Bahls

Frontlines

Seeing the Whole Picture, and Then Some

Courtesy of Jason KuslerA quarterback decides where to throw the football based on the field's layout and the players' positions on it. Scanning the field, he sees loads of images that help him make his split-second decisions. He actually views even more that he may not recall.René Marois of Vanderbilt University, Nashville, Tenn., and colleagues study the delicate balance between seeing, registering, and recalling images in the visual field. If images come faster than two per second, subje

Deducing the Brain's Evolution, Scale by Scale

Courtesy of Allen ChartierDavid Crews' lab resembles an exotic pet store; there's not a mouse or rat in sight. This professor of integrative biology at the University of Texas, Austin, studies animals such as the inches-long whiptail lizard."I'm interested in the evolution of brain mechanisms involved in social and sexual behaviors," Crews says. "You have to have ancestral species." The lizard, Cnemidophorus uniparens, reproduces parthenogenetically, though it evolved from the still extant C. in

Foundations

On the Trail of BRCA1

Courtesy of Mary-Claire KingAfter 16 years of exhausting research, data collection and computation, Mary-Claire King's lab determined in 1990 that a mutation on chromosome 17 was a common occurrence among women in families that had clusters of breast cancer. This family tree shows one of the families in the study. Squares are men, circles are women. Blackened circles indicate women with breast cancer. A cross through the symbol means that person died.When the paper was published in 1990,1 King b

First Person

Mary-Claire King

You were at Berkeley, the center of activism in the 1960s, during a tumultuous time. Do you recall it with nostalgia or regret?Courtesy of The Seattle TimesMainly pride. I don't indulge in nostalgia about that period because it was a terrible time for our country. It's very American: When you see something wrong, you try to fix it. The single most effective thing we did was on the day after the US invaded Cambodia, we got out our suit jackets and shirtwaist dresses – not clothes that any o

Research

Vax Facts

Compiled by Sam JaffeCancer vaccine therapies continue to inch toward approval. Even with the complex regulations controlling biologics and cell based techniques, over 100 such treatments are undergoing clinical trials, with more than a dozen in Phase III trials. The underlying mechanisms vary widely, but they share the goal of boosting the immune system to attack pre-existing tumors. Here are four examples of formulations that have shown some promise.Cytokine Vaccine: A whole-cell vaccine calle

Appraising Aneuploidy as a Cancer Cause

THE TRIPLETS OF CELLVILLE:(Reprinted with permission from G.A. Pihan et al., Cancer Res, 63: 1398–404, 2003)When stained with a biotinylated probe specific for the chromosome 8 centromere, diploid cells from normal human uterine cervix (A), breast (C), and prostate (E) tissue show two signals. Aneuploid cells from carcinoma tissues in situ (B, D, and F) each have three or more signals.About 70 scientists recently attended an invitation-only California premiere tinged with controversy. But

A Deadly Selection

CALCULATED ESCAPE:Adapted from Y. Iwasa, et al., Proc R soc Lond B Sci, 270: 2573–8, 2003.In this example, genes can mutate at the rate u per gene, per cell division. Gross chromosomal changes occur at the rate p. For this tumor suppressor gene, TSP, Cancer cells have two functioning alleles prior to chemotherapy. Cell reproductive rates Ro-R4 are assumed equal, and a = R/(1-R). Therefore, the critical population size before escape from the therapeutic could happen, N*, can be represented

Sensitizing Cancer Through mTOR

PROMISCUOUS PATHWAY:Courtesy of BiocartaIn addition to cell-cycle regulation, mTOR plays a role in muscle hypertrophy following increased use through the growth factor IGF-1 and tumor suppressor PTEN. Blocking mTOR with drugs like rapamycin prevents muscle growth.Rapamycin could have been an anti- than tumor contender. Indeed, for more than 30 years, researchers have sized up this immunosuppressant's potential in treating a variety of cancers, including prostate, brain, and lung. Currently, howe

Hot Paper

The Makings of a Microarray Prognosis

A TELLING EXPRESSION:© 2002 ElsevierExpression patterns for 7 and 20 genes that were selected as discriminators of relapse versus continuous complete remission (CCR) for two types of acute lymphoblastic leukemia, T-ALL and hyperdiploid >50 ALL. (from E-.J. Yeoh et al., Cancer Cell 1:133–43, 2002.)Countless things can go wrong in the complicated cell division process. Checkpoints fail, genomic instability increases, and when anarchy reigns, cancers spread. In trying to assess what is d

Briefs

Stress and Cancer: Going with the Gut

© 2004 AACRBacterially induced gut cancers may solidify the role of oxidative stress in tumorigenesis. Medical oncologist Fong-Fong Chu and colleagues at City of Hope's Beckman Research Institute, Duarte, Calif., found that mice missing the glutathione peroxi-dase genes Gpx1 and Gpx2 are more likely to get intestinal cancer if exposed to bacteria, including Helicobacter hepaticus.1Both genes protect organisms from oxidative stress, strengthening the belief, says Chu, that such stress can le

Turning Out the Pockets for Narcolepsy and Diabetes

Courtesy of Lars FuggerParadoxically, a single MHC class II allele, HLA-DQ0602, confers susceptibility to narcolepsy but prevents development of type I diabetes. Clinical immunologist Lars Fugger and structural biologist Yvonne Jones, both at Oxford University, have compared the crystal structure of the allele with those of two similar MHC molecules that respectively predispose to type 1 diabetes and protect against narcolepsy.1 They have identified unique features of several pockets within the

Interdisciplinary Research

These papers were selected from multiple disciplines from the Faculty of 1000, a Web-based literature awareness tool http://www.facultyof1000.com.B. Van den Berg et al., "X-ray structure of a protein-conducting channel," Nature, 427:36–44, Jan. 1, 2004.The first crystal structure of a protein translocation channel demonstrates the principle according to which proteins are funneled across membranes. The pore has an hourglass shape with a "plug" in the middle that probably swings out of the

Patent Watch

, Your Membrane Proteins are Showing

For those who need to express recombinant membrane proteins, the use of Escherichia coli has been problematic because these proteins are often lethal, according to Mary Lynne Collins, a professor of biology at the University of Wisconsin, Milwaukee. Collins and Yongjian Cheng were recently awarded US patent 6,680,179 for a method that allows expression of membrane proteins in Rhodospirillum rubrum, whose unique features make it an attractive host, says Collins.R. rubrum is a photosynthetic bacte

Software Watch

A Crystallographer's Little Helper

Creating a protein crystal structure diagram from raw X-ray diffraction data is a labor-intensive task that can take weeks to months. A new program called ELVES http://ucxray.berkeley.edu/~jamesh/elves from the Lawrence Berkeley National Laboratory in California automates the process and can churn out the diagram in only a few hours."When humans deal with a complex system with hundreds of things to keep track of, they make mistakes," says James Holton, the creator of the UNIX-compatible program

Tech Watch

Building a Better Buffer

Every molecular biologist knows about Tris, but few have questioned its suitability as an electrophoretic buffer component. An intrepid pair of researchers at Johns Hopkins' Sidney Kimmel Comprehensive Cancer Center have studied Tris and found it to be lacking.1No paper has ever claimed that Tris was the best buffer, says Scott Kern, professor of oncology and pathology. "It's just something that somebody once used, then somebody else used it, and pretty soon you had a herd mentality." Tris buffe

Technology

Advances in Cellular Image Processing

EMBRYOGENESIS UNFOLDING IN 3-D:Left and Right Image: Courtesy of Wen Bin Tsai & W. Kinsey Center image: Courtesy of H. Matsumoto & S. K. DeyThree-dimensional projections created from Z-stacks of a zebrafish embryo at the four-cell stage (left), a blastocyst (center), and a more fully developed zebrafish embryo (right). DAPI-stained nuclei are colored blue, while various specific proteins are labeled green (FITC/FITX) and red (rhodamine).Like much of science, imaging has become almost ent

TMA Buyers' Guide

Courtesy of Ronald Simon, University of BaselBarely five years ago, Juha Kononen, then at the National Cancer Institute, presented a straightforward way of constructing tissue microarrays (TMAs): a glass slide covered with as many as 1,000 cores of tissue, measuring from 0.6 mm to 2.0 mm in diameter.1 Suddenly, researchers could analyze gene expression and protein levels on hundreds of tissue samples by processing just one slide, instead of the hundreds previously required. As a result, scientis

Tools and Technology

Drosophila

IMAGE OF AN ADULT FLY BRAIN:Courtesy of Diane O'DowdO'Dowd's team measured neuronal activity from the central brain region, which is flanked on either side by the visual lobes and eyes (red).Drosophila, the winged workhorse of biology, has reached another milestone. Recently several labs have recorded electrophysiological data from the fly's central nervous system (CNS) neurons. "Drosophila is one of the most powerful neurobiological model systems around. The only thing it lacked was direct acce

SEM Goes Live

Courtesy of QuantomiXThe ultrahigh resolution of scanning electron microscopy (SEM) makes it a powerful tool for examining microstructures. But while SEM is a great way to study the surface of a crystal or a silicon chip, its application to the life sciences has lagged far behind its usefulness in materials science and crystallography.SEM samples must generally be imaged in a vacuum, which is not a friendly place for cells. Moreover, traditional methods of preparing wet samples for the vacuum ch

Refreshing Idea for Growth

Courtesy of GenetixStandard mammalian tissue culture techniques usually require growth media refreshment every two to three days, accomplished by manually pouring or pipetting off the old medium and replacing it with new. To circumvent this tedious process, New Milton, UK-based Genetix http://www.genetix.co.uk recently launched QFresh, the first instrument designed for the automatic exchange of culture media in petri dishes.The programmable instrument does it all: A mechanical apparatus removes

Arraying Archives

Microarray manufacturer Affymetrix of Santa Clara, Calif., http://www.affymetrix.com and laser-capture microdissection company Arcturus of Mountain View, Calif. http://www.arctur.com, have teamed up, offering the GeneChip X3P array and the Paradise™ reagent system, respectively, to enable gene expression analysis of archived formalin-fixed, paraffin-embedded (FFPE) samples. "These samples represent a treasure trove for genomic discovery efforts, because they generally are associated with k

Tip Trove

Good Teaching Equals Learning

1. Get to know your studentsBy knowing the extent of your students' current knowledge of the subject, you can more effectively present what they need to know in ways they will understand. A pre-test can give you excellent information about the students' knowledge base. Encourage the students to come talk to you during office hours. Meet with the students in small groups at the beginning of the semester to get to know them and talk about your expectations of them and their expectations for the cl

Data Points

Cancer Spotlight

UNITED STATESCompiled by Francesco FiondellaThe National Institutes of Health is the biggest funder of cancer research in the US. Figures include grants, contracts and intramural research.UNITED KINGDOMThe National Cancer Research Institute tracks funding given out by the UK's major cancer centers. Below, research spending in 2002.††Projects ongoing on April 2002 (most recent data available). Figures exclude overhead, marketing, etc.NOTE: Fiscal years used throughout. Figures for Bri

Profession

Cell Biologist Multitasks for Women

Mary OsbornCourtesy of Mary OsbornMary Osborn helped pioneer immunofluorescence microscopy, and in her images, the three-dimensional cells dance across a black screen in flecks of colored light, helping scientists see new aspects to diseases such as muscular dystrophy and cancer. Her diligence and focus in pursuing this technology for understanding cell structures has provided her a place among Europe's most prominent scientists: She ranked among the most highly cited researchers during the earl

Biodefense Squeezes US Science Budgets

Francesco FiondellaWhen he addressed the nation in January, President George W. Bush left little doubt that he intends to invest enormous amounts of federal cash into homeland security, including efforts to protect Americans from bioterrorism. What the president did not say during his annual State of the Union speech was where the funds will come from.The federal budgets for FY2004 and FY2005 reflect a fundamental shift in White House priorities when it comes to scientific research, one that foc

Funding Deters Scientists from Developing New Models

In the 1950s, a young psychiatrist sought an animal with neurons large enough for electrophysiology experiments on learning and memory. The animal, Aplysia californica, eventually got dissected in neurobiology labs around the world. The psychiatrist fared a little better; he was awarded the Nobel Prize.The tale of Eric Kandel and Aplysia, like that of Thomas Hunt Morgan and Drosophila or Sydney Brenner and Caenorhabditis elegans, has become a scientific bedtime story. The moral: Choose the right

How to Be a Cancer Entrepreneur

Photo courtesy of ChemGenex TherapeuticsDennis Brown left an assistant professorship at Harvard's Joint Center for Radiation in 1988 to start Matrix Pharmaceuticals. When that company sold, Brown's inner entrepreneur led him to create ChemGenex in 1999. The company works with small-molecule therapies and has two in Phase I and II clinical trials for cancer. "The first company did what it set out to do," Brown says. "Many people got significant training and went on to start their own companies."P

Postdoc Talk

Man Bests Machine, This Time

Courtesy of Asaph CousinsCommon knowledge says that the more expertise scientists gain in their specializations, the less they know about anything else. I know plant physiology: Biochemical assays, chlorophyll fluorescence, and gas analyzers comprise my world. Yet here I am, facing off with a malfunctioning heap of electrical gadgetry, armed with a soldering iron, voltage meter, and lab goggles.Taming a tangled web of wire and conduit was not in today's game plan. I intended to use the instrumen

Science Rules

Peers Ponder Review

File PhotoThe peer-review system of the German Research Foundation (DFG) is unique, as proposals are reviewed by experts nominated and elected by the scientific community. This will change in the spring, however, when the DFG will select the reviewers; the elected representatives will be responsible for quality control and for writing funding recommendations based on the initial reviews. The DFG claims that the reform strengthens the principle of academic self-government, but critics of the new

Closing Bell

The Impossible Dream of Eliminating the Nobel Prize

Given the reverence that the Nobel science prizes command, there's but a scant chance that the century-old awards will be deservedly terminated for what they've become: anachronisms that caricature the workings of modern research and sow acrimony among scientists.The turbo-hyped Nobels annually bring luster to Sweden, where the king hands out $1 million prizes in a ceremonial setting that draws prime-time attention worldwide. As one of the biggest, oldest, and most mystique-bound awards, the pri