Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Materials Scientist Seeks Dwarfism Clues in a Cell’s Membrane

23.08.2010
Achondroplasia, a common form of dwarfism, is caused by a genetic mutation: A single incorrect building block in a strand of DNA produces a defective protein that disrupts normal growth. If a scientist could figure out precisely how this errant protein causes trouble, then a way to avert this chain of events might be found.

Sounds like a job for a biologist. Or maybe not. The person who cracks this mutation mystery might just be a Johns Hopkins engineer who works with cell membranes.

Kalina Hristova, an associate professor of materials science and engineering, has spent more than five years in a nontraditional effort to understand how that tiny DNA error leads to dwarfism. Hristova, an expert in the field of membrane biophysics, has focused her research on the thin protective covering that surrounds human cells, the plasma membrane; for this project, she is studying the activity of proteins that reside in this membrane. Among these proteins is the one linked to dwarfism.

A biologist might attack this puzzle by growing cells in a dish or conducting experiments with lab animals. Hristova, supported by a federal stimulus grant, instead has been using engineering tactics to determine how the protein may be wreaking havoc. Her lab has developed new tools and techniques that allow her to take pictures and make measurements that reveal how the rogue protein is behaving in the cell membrane. Her team’s goal is to generate exact numbers that will yield clues about how the protein causes the cells to take a wrong turn.

“Unlike the biologists, we are not investigating what will happen to the cell in 20 days,” she said. “We are looking at the initial events occurring in the cell membrane, the way proteins first interact there. As engineers, we have to strip down the system and simplify it so that we can see how it works. We are looking at the physics, not the biology.”

For her project, called “Seeking the Physical Basis of Achondroplasia,” Hristova has received a $27,000 federal stimulus grant for lab equipment, which supplements her five-year grant of approximately $1 million from the National Institutes of Health. Her award is among the 424 stimulus-funded research grants and supplements totaling more than $200 million that Johns Hopkins has garnered since Congress passed the American Recovery and Reinvestment Act of 2009, bestowing the NIH and the National Science Foundation with $12.4 billion in extra money to underwrite research grants by September 2010.

Achondroplasia, the focus of Hristova’s grant, is the most common form of short-limbed dwarfism, occurring in one in 15,000 to 40,000 newborns worldwide, according to the National Institutes of Health. The condition results from a mutated FGFR3 gene. In some cases, this mutation is passed down by at least one parent. But about 80 percent of those with achondroplasia have average-size parents and develop the condition because a new mutation occurs. This defective gene produces proteins that send “stop” signals, halting the growth of cartilage that makes room for normal-size long bones of the arms and legs.

Hristova cautions that no “cure” for achondroplasia exists and that her research is unlikely to produce one in the near future. She describes her work as basic research that could lay the groundwork for future treatment or prevention of achondroplasia.

“Finding the cause of this condition is a very hard problem, because the first thing you need to do is to understand what’s happening at the molecular level, what these proteins are actually doing,” she said. “Before you can solve a problem, you need to know what’s causing it.”

The proteins Hristova is examining are tiny threads of amino acids embedded in the cell membrane, with one end extending inside the cell and the other wriggling outside. This arrangement allows the protein to gather information outside the cell and send messages to the nucleus, or control center, inside the cell. These messages provide instructions to the cell, including telling it whether or not to grow.

To find out how this process goes awry in people with dwarfism, Hristova is investigating how the mutated protein is embedded within the membrane, compared to the proteins of people who grow normally. Does one type stick farther inside or outside the cell? She also is trying to determine whether the growth disorder is related to the chemical and mechanical ways that the mutated proteins “talk” to other proteins in the cell membrane.

To conduct these studies, Hristova and her team coax cells into making the protein, then “trick” the cells into giving up their membranes with the proteins still embedded in the material. The researchers then use a confocal microscope to gather information about the mutated proteins in these membrane segments without the constant turnover of molecules that occurs in an intact living cell. Her team also works with National Institute of Standards and Technology scientists in using a technology called neutron diffraction to collect images that show where the proteins are situated with respect to the membrane’s surface.

“We are using materials science techniques to conduct innovative research into why this form of dwarfism is occurring,” Hristova said.

Hristova, whose parents are scientists, said that her entry into the field of membrane biophysics occurred “sort of by chance.” In her native Bulgaria, while earning her undergraduate and master’s degrees in physics, she became interested in biophysics. At one point, an instructor assigned her work on membranes, and she quickly embraced this area of research.

She came to the United States to pursue a doctorate in engineering and materials science at Duke, and then further honed her research skills as a postdoctoral fellow at UC Irvine. In 2001, she joined the faculty of the Whiting School of Engineering at Johns Hopkins, where she specializes in membrane biophysics and biomolecular materials and is an affiliate of the Institute for NanoBioTechnology. In 2007, Hristova received the Biophysical Society’s Margaret Oakley Dayhoff award for “her extraordinary and outstanding scientific achievements in biophysics research.”

Her interest in the dwarfism mutation originated years ago when a physician talked to her about the problem and sparked her interest in finding a solution through engineering techniques. In recent years, she has presented her findings at scientific conferences attended mainly by researchers who continue to study the disorder with the tools of a biologist.

“Eventually, sometime in the future, both approaches will come together as we work toward a basic understanding of what causes achondroplasia,” Hristova said. “Then someone will come up with a treatment.”

Photos of Kalina Hristova and her lab team available; contact Phil Sneiderman.

Related websites:
Kalina Hristova’s Lab: http://bmmb-lab.com
Johns Hopkins Department of Materials Science and Engineering: http://materials.jhu.edu

Johns Hopkins Institute for NanoBioTechnology: http://inbt.jhu.edu/

Phil Sneiderman | Newswise Science News
Further information:
http://www.jhu.edu

More articles from Materials Sciences:

nachricht Nagoya physicists resolve long-standing mystery of structure-less transition
21.08.2017 | Nagoya University

nachricht Scientists from the MSU studied new liquid-crystalline photochrom
21.08.2017 | Lomonosov Moscow State University

All articles from Materials Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Nagoya physicists resolve long-standing mystery of structure-less transition

21.08.2017 | Materials Sciences

Chronic stress induces fatal organ dysfunctions via a new neural circuit

21.08.2017 | Health and Medicine

Scientists from the MSU studied new liquid-crystalline photochrom

21.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>