Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Materials Scientist Seeks Dwarfism Clues in a Cell’s Membrane

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:
Johns Hopkins Department of Materials Science and Engineering:

Johns Hopkins Institute for NanoBioTechnology:

Phil Sneiderman | Newswise Science News
Further information:

More articles from Materials Sciences:

nachricht From ancient fossils to future cars
21.10.2016 | University of California - Riverside

nachricht Study explains strength gap between graphene, carbon fiber
20.10.2016 | Rice 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: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Ice shelf vibrations cause unusual waves in Antarctic atmosphere

25.10.2016 | Earth Sciences

Fluorescent holography: Upending the world of biological imaging

25.10.2016 | Power and Electrical Engineering

Etching Microstructures with Lasers

25.10.2016 | Process Engineering

More VideoLinks >>>