Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular machine may lead to new drugs to combat human diseases

21.02.2005


The crystallized form of a molecular machine that can cut and paste genetic material is revealing possible new paths for treating diseases such as some forms of cancer and opportunistic infections that plague HIV patients.



Purdue University researchers froze one of these molecular machines, which are chemical complexes known as a Group I intron, at mid-point in its work cycle. When frozen, crystallized introns reveal their structure and the sites at which they bind with various molecules to cause biochemical reactions. Scientists can use this knowledge to manipulate the intron to splice out malfunctioning genes, said Barbara Golden, associate professor of biochemistry. Normal genes then can take over without actually changing the genetic code.

The results of the Purdue study are published in the January issue of the journal Nature Structural and Molecular Biology. "In terms of human health, Group I introns are interesting because they cause their own removal and also splice the ends of the surrounding RNA together, forming a functional gene," Golden said. "We can design introns and re-engineer them so they will do this to RNA in which we’re interested."


Once thought of as genetic junk, introns are bits of DNA that can activate their own removal from RNA, which translates DNA’s directions for gene behavior. Introns then splice the RNA back together. Scientists are just learning whether many DNA sequences previously believed to have no function actually may play specialized roles in cell behavior.

While humans have introns, they don’t have Group I introns. Many pathogens that cause human diseases, however, do have Group I introns, including the HIV opportunistic infections pneumocystis, a form of pneumonia, and thrush, an infection of tissues in the oral cavity. This makes introns a potential target for therapeutics against these diseases by using a strategy called targeted trans-splicing in which introns are manipulated to cut out malfunctioning genes.

Introns’ unique capability of cutting and pasting apparently has been conserved since life evolved. "It’s thought that RNA, or a molecule related to RNA, possibly were the first biomolecules, because they are capable of both performing work and carrying around their own genetic code," Golden said.

She and her research team used an intron from a bacteriophage, a molecule that attacks bacteria, to obtain an intron crystal structure trapped in the middle of the cutting and pasting cycle. As introns proceed through their work cycle, they change shape by folding and bending. By crystallizing the complex at various stages, the scientists can determine and study its three-dimensional structure and learn how it is able to carry out its biochemical work.

The Group I intron at its work cycle’s mid-point, which Golden crystallized, is unreactive but reveals many of the interactions between the RNA and the molecules that it activates, she said. "Knowing the structure can help us engineer molecules to behave better," Golden said. "It’s very hard to find targets in cells because cells are organized in ways we still don’t fully understand. This crystal structure shows us where the best targets are for modifying genetic defects."

The crystal structure of this Group I intron also will allow scientists to form models of hundreds of other introns in the same family and provide possibilities for new treatments for a wide variety of diseases, she said. Other scientists now will use the information gleaned from this study in an attempt to develop new drugs, Golden said. Introns were unknown until the late 1970s, and scientists are still investigating their function. Crystallization of the complex is one tool to determine their purpose.

Two intron structures in different stages of the cycle have been crystallized previously, and the targeted trans-splicing technique has been used to repair hemoglobin infected with sickle cell anemia. The new structure provides scientists with tools to expand on ways to harness this molecular machine, Golden said.

The other researchers on this study were Hajeong Kim, graduate student, and Elaine Chase, research associate, both of the Purdue Department of Biochemistry. Golden also is a scientist in the Purdue Cancer Center, a National Cancer Institute designated research facility.

Grants from NASA, the Pew Scholars Program in Biomedical Sciences and the Purdue Cancer Center provided funding for this research.

Barbara Golden | EurekAlert!
Further information:
http://www.purdue.edu

More articles from Life Sciences:

nachricht Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen

nachricht New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Unraveling the nature of 'whistlers' from space in the lab

15.08.2018 | Physics and Astronomy

Diving robots find Antarctic winter seas exhale surprising amounts of carbon dioxide

15.08.2018 | Earth Sciences

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>