Spying on a Cellular Director in the Cutting Room

Like a film director cutting out extraneous footage to create a blockbuster, the cellular machine called the spliceosome snips out unwanted stretches of genetic material and joins the remaining pieces to fashion a template for protein production.


But more than box office revenues are at stake: if the spliceosome makes a careless cut, disease likely results.

Using a new approach to studying the spliceosome, a team led by University of Michigan chemistry and biophysics professor Nils Walter, collaborating closely with a team led by internationally recognized splicing experts John Abelson and Christine Guthrie of the University of California, San Francisco, spied on the splicing process in single molecules.

The research is scheduled to be published online March 21 in Nature Structural and Molecular Biology.

Since its Nobel Prize-winning discovery in 1977, gene splicing has been studied in a number of organisms, including yeast and human cells, using both genetic and biochemical approaches. While these methods can yield snapshots, they can't monitor the ongoing process. The new study, which utilizes a technique called fluorescence resonance energy transfer (FRET) and a sophisticated microscope that watches single molecules in action, allows researchers to observe in real time the contortions involved in spliceosome assembly and operation.

Read more »

Wide Variety of Genetic Splicing in Embryonic Stem Cells Identified

Like tuning in to an elusive radio frequency in a busy city, human embryonic stem cells must sort through a seemingly endless number of options to settle on the specific genetic message, or station, that instructs them to become more-specialized cells in the body (Easy Listening, maybe, for skin cells, and Techno for neurons?). Now researchers at the Stanford University School of Medicine have shown that this tuning process is accomplished in part by restricting the number of messages, called transcripts, produced from each gene.


Most genes can yield a variety of transcripts through a process called splicing. Variations in the ways a gene is spliced can change the form and function of the final protein product. Nearly all our genes can be spliced in more than one way. This research is the first time, however, that splicing variety has been linked to the unprecedented developmental flexibility, or pluripotency, exhibited by embryonic stem cells.

"The embryonic stem cells are loaded with many splicing variants for each gene," said Michael Snyder, PhD, chair of Stanford's genetics department. "But as the cells differentiate and become more specialized, the number of types of transcripts decreases."

Snyder and his colleagues studied the changes in RNA transcript levels occurring as the embryonic stem cells were induced in a laboratory dish to differentiate into neural cells. (The creation of RNA transcripts is an intermediate step in the generation of proteins from DNA.) In the process they generated a unique "dictionary" of neural-specific splicing variants, or isoforms.

Read more »

'Doublesex' Gene Key to Determining Fruit Fly Gender

The brains of males and females, and how they use them, may be far more different then previously thought, at least in the fruit fly Drosophila melanogaster, according to research funded by the Wellcome Trust.

In a paper published in the journal Nature Neuroscience, researchers from the University of Glasgow and the University of Oxford, have shown that the gene known as 'doublesex' (dsx), which determines the shape and structure of the male and female body in the fruit fly, also sculpts the architecture of their brain and nervous system, resulting in sex-specific behaviours.

The courtship behaviour of the fruit fly has long been used to study the relationship between genes and behaviour: it is innate, manifesting in a series of stereotypical behaviours largely performed by the male. The male chases an initially unreceptive female, and 'woos' her through tapping and licking and using wing vibration to generate a 'courtship' song. If successful, the female will slow and present a receptive posture, which allows copulation to occur.

For some time now, the gene 'fruitless' (fru), which is specific to the adult male fruit fly, was thought to be the key to male behaviour and the development of male specific neural circuitry of flies.

Read more »

Bio Weapons

Rapid developments in biotechnology, genetics and genomics are undoubtedly creating a variety of environmental, ethical, political and social challenges for advanced societies. But they also have severe implications for international peace and security because they open up tremendous avenues for the creation of new biological weapons.

The genetically engineered 'superbug'—highly lethal and resistant to environmental influence or any medical treatment—is only a small part of this story. Much more alarming, from an arms-control perspective, are the possibilities of developing completely novel weapons on the basis of knowledge provided by biomedical research—developments that are already taking place.

Such weapons, designed for new types of conflicts and warfare scenarios, secret operations or sabotage activities, are not mere science fiction, but are increasingly becoming a reality that we have to face. Here, we provide a systematic overview of the possible impact of biotechnology on the development of biological weapons.


The history of biological warfare is nearly as old as the history of warfare itself. In ancient times, warring parties poisoned wells or used arrowheads with natural toxins. Mongol invaders catapulted plague victims into besieged cities, probably causing the first great plague epidemic in Europe, and British settlers distributed smallpox-infected blankets to native Americans.


Indeed, the insights into the nature of infectious diseases gained by Louis Pasteur and Robert Koch in the nineteenth century did not actually represent a great breakthrough in the use of infectious organisms as biological weapons. Similarly, the development of a bioweapon does not necessarily require genetic engineering—smallpox, plague and anthrax are deadly enough in their natural states. But the revolution in biotechnology, namely the new tools for analysing and specifically changing an organism's genetic material, has led to an increased risk of biowarfare due to several factors.

First, the expansion of modern biotechnology in medical and pharmaceutical research and production has led to a worldwide availability of knowledge and facilities. Many countries and regions, where 30 years ago biotechnology merely meant brewing beer and baking bread, have established high-tech facilities for vaccine or single-cell-protein production that could be subverted for the production of biological weapons. Today, nearly all countries have the technological potential to produce large amounts of pathogenic microorganisms safely.


Second, classical biowarfare agents can be made much more efficiently than their natural counterparts, with even the simplest genetic techniques.

Third, with modern biotechnology it becomes possible to create completely new biological weapons. And for technical and/or moral reasons, they might be more likely to be used than classical biowarfare agents. These possibilities have generated new military desires around the world, including within those countries that have publicly renounced biological weapons in the past.


This paper deals predominantly with the last two factors, and with the use of real-life examples, we shall discuss the possibilities for such military abuse of biotechnology.

Read more »

Biological Weapons

Biological Weapons

There are a variety of microorganisms that can be used as biological weapons. Agents are commonly chosen because they are highly toxic, easily obtainable and inexpensive to produce, easily transferable from person to person, can be dispersed in aerosol form, or have no known vaccine. Below is a list of a few potential biological organisms that may be used as biological weapons.

Read more »