Nav: Home

New platform for roundworms could speed up drug delivery

October 11, 2016

Researchers in the Cockrell School of Engineering at The University of Texas at Austin have developed the first large-scale in vivo drug discovery platform using a whole animal model that could speed up scientific research and more accurately assess the effectiveness of new drugs in the treatment of neurodegenerative diseases.

Professor Adela Ben-Yakar and her team of postdocs and graduate students -- Sudip Mondal, Evan Hegarty, Christopher Martin, Sertan Kutal Gökçe and Navid Ghorashian -- describe their new platform in a study published in the journal Nature Communications on Oct. 11.

The team believes their platform will allow researchers and pharmaceutical companies to undertake image-based analysis of thousands of live, 1-millimeter-long roundworms, called Caenorhabditis elegans (C. elegans), simultaneously and at the speed and cost of in vitro cell-based platforms.

Ben-Yakar, a researcher in the Departments of Mechanical and Biomedical Engineering, led the design of the new platform, which takes the form of a cellphone-size chip that can immobilize and analyze small animal models using a high-powered microscope. The platform is similar to screening platforms for cells, but it can screen a whole organism made of multiple cells by immobilizing thousands of them inside micro-traps to prevent their natural movement. In addition, the platform can automatically understand data using image analysis software, which was also developed by the researchers. This information can help determine whether a drug is effectively treating a disease in the roundworms.

The researchers' microfluidic device is designed to simultaneously image approximately 3,600 roundworms at high resolutions and high speeds, ranging from 12 to 16 minutes. Today's conventional platforms can image only a few animals within such a short time. The device also has the ability to assess the efficacy of many different drug compounds at once. Whereas other microfluidic platforms used today are capable of analyzing only one drug compound at a time, the researchers' new platform can assess 96.

The roundworms, which are desirable in the study of neurodegenerative diseases because they have full nervous systems and a diverse group of neurons, are also the first multicellular organism to have a completely sequenced genome. Approximately one-third of C. elegans' genes are the same as disease-causing genes in humans.

"The C. elegans are thousands of times bigger than cells, so now that we have developed a way to capture and immobilize so many of them so quickly, we can determine much more information about the efficacy of drugs in a whole organism rather than the limited information that is derived when we used isolated individual cells," Ben-Yakar said.

What sets the chip apart from existing platforms is that it is capable of high-throughput screening, the study of thousands to hundreds of thousands of compounds in a rapid and very high-resolution manner, and high-content fluorescence screening, which allows for a faster yet more in-depth analysis of the animals' phenotype.

Made of a flexible polymer, the microfluidic chip contains 96 wells for receiving drug-treated animals. Underneath each well are special microchannels that can trap 40 roundworms. A tapered design squeezes the C. elegans into microchannels in a flat orientation that can be more easily imaged. The microfluidic chip then relies on a gasket system that applies pressure to the chambers to immobilize the roundworms.

"This proof-of-principle study opens the door to using this technology to identify and develop treatments for some of the most intractable human diseases," said Anne Hart, a professor of neuroscience at Brown University who has followed the development of the chip.

To demonstrate the efficiency of their patent-pending device, the team analyzed approximately 1,000 drugs approved by the Food and Drug Administration aimed at treating the protein aggregation found in various neurodegenerative diseases, including Huntington's disease. In doing so, they were surprised to find a potential drug that is particularly effective at treating Huntington's.

"Four of the drugs we tested were effective at treating a protein aggregation model that is directly related to Huntington's, and one of these drugs became even more effective at increased doses without causing toxicity," Ben-Yakar said.

Although the microfluidic device is a prototype, Ben-Yakar's startup company, Newormics, is working to develop a design for a commercial product that could be cheaply and easily manufactured.
This work received funding from the National Institutes of Health (NIH) Director's Transformative Award, National Institute on Aging (NIH/NIA R01).

University of Texas at Austin

Related Neurodegenerative Diseases Articles:

New family of molecules to join altered receptors in neurodegenerative diseases
An article published in the Journal of Medicinal Chemistry shows a new family of molecules with high affinity to join imidazoline receptors, which are altered in the brain of those patients with neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's.
Examining diagnoses of stress-related disorders, risk of neurodegenerative diseases
Researchers investigated how stress-related disorders (such as posttraumatic stress disorder, adjustment disorder and stress reactions) were associated with risk for neurodegenerative diseases, including Alzheimer and Parkinson disease and amyotrophic lateral sclerosis (ALS), using data from national health registers in Sweden.
Toxic protein, linked to Alzheimer's and neurodegenerative diseases, exposed in new detail
The protein tau has long been implicated in Alzheimer's and a host of other debilitating brain diseases.
Study uncovers unexpected connection between gliomas, neurodegenerative diseases
New basic science and clinical research identifies TAU, the same protein studied in the development of Alzheimer's, as a biomarker for glioma development.
Neurodegenerative diseases may be caused by transportation failures inside neurons
Protein clumps are routinely found in the brains of patients with neurodegenerative diseases.
Study suggests a protein could play key role in neurodegenerative diseases
Research led by Queen Mary University of London and the University of Seville around one protein's role in regulating brain inflammation could improve our understanding of neurodegenerative diseases.
Beyond finding a gene: Same repeated stretch of DNA in three neurodegenerative diseases
Four different rare diseases are all caused by the same short segment of DNA repeated too many times, a mutation researchers call noncoding expanded tandem repeats.
Protein complex may help prevent neurodegenerative diseases
The protein complex NAC in the cell helps to prevent the aggregration of proteins associated with several neurodegenerative diseases.
Experimental Biology highlights -- Cancer, neurodegenerative diseases and medical news
Embargoed press materials are now available for the Experimental Biology (EB) 2019 meeting, to be held in Orlando April 6-9.
Circadian clock plays unexpected role in neurodegenerative diseases
Northwestern University researchers induced jet lag in a fruit fly model of Huntington disease and found that jet lag protected the flies' neurons.
More Neurodegenerative Diseases News and Neurodegenerative Diseases Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at