Biochip quickly tests results of cancer therapy

The inside structure of the biochip is comprised of 3 layers, each testing a key element of the therapy: drug, oxygen, and light. (Credit: Xia Lou/University of Michigan)


University of Michigan right Original Study ("A high-throughput photodynamic therapy screening platform with on-chip control of multiple microenvironmental factors")

A new type of lab-on-a-chip could make it easier to determine the effectiveness of a promising cancer treatment that combines photosensitive drugs, light, and oxygen.

The treatment, known as photodynamic therapy (PDT), uses a unique type of drug, called a photosensitizer, that generates high-energy oxygen when activated by light, in this case an LED laser.

The oxygen reaction destroys cells locally only in the immediate surrounding area, which in this case is the tumor, without damaging other healthy cells in the rest of the body. PDT may also prompt the patient’s immune system to attack the tumor, whereas without treatment it will likely ignore it.

“PDT is a fairly complicated therapy because it requires light, oxygen, and the drug, all three of which need to be carefully controlled,” says Xia Lou, a postdoctoral fellow at the University of Michigan. “With chemotherapy, for example, you only control how much of the drug is used.”

The biochip can test the interaction of the drug, light, and oxygen simultaneously, generating results in a fraction of the time of current testing practices.

“In cancer research doctors are always looking for better drugs,” adds Lou. “But there has always been a lack in the ability to efficiently test new drugs.

“Researchers are also hoping to get more reliable test results than is the norm. We are providing more precise drug test conditions to insure that the results we are getting will more closely match the actual results from cancer treatment.”

Test all three components There are two primary challenges in PDT today:

• One is determining the best treatment plan for the patient, and 
• the other is testing the efficacy of new and existing drugs.

For example, the location of a tumor in the body will determine the amount of light needed to excite the drug, and will impact the amount of drug that is administered. Also, when testing new drugs, it is again important to know the amount of light needed to excite the oxygen reaction, and the strength of the reaction.

This adds a high level of complexity compared to conventional drug testing that only tests one component, the drug itself.

Current PDT testing methods might take more than 24 hours to acquire just 10 data points.

“With our device,” says Lou, “we can finish the testing in 1 hour and have 1,000 data points. The result is a very comprehensive understanding of how the 3 elements need to be manipulated for maximum effect in an individual patient.”

The researchers reported the details of their findings in the journal Lab on a Chip. The NSF Engineering Research Center for Wireless Integrated Microsystems, Thermo Fisher Scientific, and the National Institute of Health supported the project.

Source: University of Michigan

ORIGINAL: Futurity

by Catharine June-U. Michigan 

February 28, 2014 

Scientists discover double meaning in genetic code

Scientists have discovered a second code hiding within DNA. This second code contains information that changes how scientists read the instructions contained in DNA and interpret mutations to make sense of health and disease.

Genome scientist Dr. John Stamatoyannopolous led
a team that discovered a second code hidden in DNA

A research team led by Dr. John Stamatoyannopoulos, University of Washington associate professor of genome sciences and of medicine, made the discovery. The findings are reported in the Dec. 13 issue of Science. The work is part of the Encyclopedia of DNA Elements Project, also known as ENCODE. The National Human Genome Research Institute funded the multi-year, international effort. ENCODE aims to discover where and how the directions for biological functions are stored in the human genome.

Since the genetic code was deciphered in the 1960s, scientists have assumed that it was used exclusively to write information about proteins. UW scientists were stunned to discover that genomes use the genetic code to write two separate languages.

• One describes how proteins are made, and the 
• other instructs the cell on how genes are controlled. 

One language is written on top of the other, which is why the second language remained hidden for so long.

“For over 40 years we have assumed that DNA changes affecting the genetic code solely impact how proteins are made,” said Stamatoyannopoulos. “Now we know that this basic assumption about reading the human genome missed half of the picture. These new findings highlight that DNA is an incredibly powerful information storage device, which nature has fully exploited in unexpected ways.”

The genetic code uses a 64-letter alphabet called codons. The UW team discovered that some codons, which they called duons, can have two meanings, 

• one related to protein sequence, and 
• one related to gene control. 

These two meanings seem to have evolved in concert with each other. The gene control instructions appear to help stabilize certain beneficial features of proteins and how they are made.
The discovery of duons has major implications for how scientists and physicians interpret a patient’s genome and will open new doors to the diagnosis and treatment of disease.

“The fact that the genetic code can simultaneously write two kinds of information means that many DNA changes that appear to alter protein sequences may actually cause disease by disrupting gene control programs or even both mechanisms simultaneously,” said Stamatoyannopoulos.

Grants from the National Institutes of Health U54HG004592, U54HG007010, and UO1E51156 and National Institute of Diabetes and Digestive and Kidney Diseases FDK095678A funded the research.

In addition to Stamatoyannopoulos, the research team included Andrew B. Stergachis, Eric Haugen, Anthony Shafer, Wenqing Fu, Benjamin Vernot, Alex Reynolds, and Joshua M. Akey, all from the UW Department of Genome Sciences, Anthony Raubitschek of the UW Department of Immunology and Benaroya Research Institute, Steven Ziegler of Benaroya Research Institute, and Emily M. LeProust, formerly of Agilent Technologists and now with Twist Bioscience.

ORIGINAL: U of Washington

UW Health Sciences and UW Medicine

December 12, 2013

The 2012 Bio-Art Winners (detailed)

ORIGINAL: FASEB

This images are so stunning that deserved another post

Frank Moutos and Farshid Guilak*

Duke University Medical Center, Durham, NC

Due to a lack of blood vessels and other characteristics, cartilage heals very slowly. One way to accelerate natural cartilage repair and growth is to use tissue engineering, or the artificially-stimulated production of functional replacement tissue. The image shows a three-dimensionally woven biomaterial scaffold. The scaffold consists of multiple layers of resorbable fiber bundles that have been woven into a porous structure. The scaffold is then seeded with cells that grow to become new tissue as the fibers are resorbed. The fibers provide stiffness and strength in a manner that mimics native collagenous tissues such as cartilage. This work to use tissue engineering to generate replacement cartilage is supported by NIH funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

*Biomedical Engineering Society

Douglas B. Cowan†*

Harvard Medical School, Boston, MA

This micrograph shows cells called myoblasts attached to spherical microcarriers, which allow the growth of adult stem cells that have been isolated from skeletal muscle. The stem cells are shown in green. By combining these cells in a bioreactor, the muscle stem cells can be greatly increased in number and then separated from the myoblast “feeder” cells. The image was produced in the course of studies aimed at creating artificial “stem cell factories” and was supported by NIH funding from the National Heart, Lung and Blood Institute.

†American Physiological Society

*Biomedical Engineering Society

Matthew E. Arnegard1, Derrick J. Zwickl2, Ying Lu3, and Harold H. Zakon3

1Fred Hutchinson Cancer Research Center, Seattle, WA

2University of Kansas, Lawrence, KS

3University of Texas, Austin, TX

Closely related electric fish species from the Okano River of Gabon, collected in the vicinity of the abandoned Fang village, “Na.” Each species is shown along with a recording of its electric organ discharge, which these fish use to communicate with one another and electro-locate prey, much like bats use echolocation. Electric fish recognize other members of their own species using the species-specific waveforms of these heartbeat-like discharges. NIH funding from the National Institute of General Medical Sciences allows Arnegard and colleagues to investigate how this electrical variability is caused by some of the same genetic mutations that, in humans, lead to congenital heart defects and childhood epilepsy.

Ivica Grgic1,2, Craig R. Brooks1, Andreas F. Hofmeister1,2, Vanesa Bijol1, Joseph V. Bonventre1,3,4†‡, and Benjamin D. Humphreys1,4

1Harvard Medical School, Boston, MA

2Philipps-University, Marburg, Germany

3Harvard University-Massachusetts Institute of Technology, Cambridge, MA

4Harvard University, Cambridge, MA

Visualizing the smallest biological structures has traditionally required the use of highly specialized electron microscopy equipment. Using a combination of genetic-based labeling and a variety of fluorescent proteins, researchers have developed a way to push the limits of the light microscope to view the smallest of biological structures. The image shows foot processes of genetically labeled cells (red) covering walls of capillaries (green) in a kidney of a mouse. This work is supported by the NIH National Institute of Diabetes and Digestive and Kidney Diseases.

†American Physiological Society

‡American Society for Clinical Investigation

Submission by The American Association of Immunologists on behalf of Mohammed Khan1, Theodore S. Steiner2, Ho Pan Sham1, Kirk S. Bergstrom1, Jingtian T. Huang1, Kiran Assi2, Bill Salh2†, Isabella T. Tai2, Xiaoxia Li3**††, and Bruce A. Vallance1†††

1British Columbia Children's Hospital, Vancouver, Canada

2University of British Columbia, Vancouver, Canada

3Cleveland Clinic Foundation, Cleveland, OH

The control of inflammatory responses in the intestinal lining is critical to the prevention of unwanted immune reactions to the “good bacteria” in the gut. Expressed on the surface of the cells of the intestine, the single IgG IL-1-related receptor (Sigirr) is a key regulator of this process. Tissue from a colon biopsy stained for Sigirr and other cellular components is shown. Therapeutic targeting of Sigirr could be useful in the treatment of inflammatory bowel disease or other inflammatory disorders of the gastrointestinal tract.

†American Physiological Society

**American Society for Biochemistry & Molecular Biology

††The American Association of Immunologists

Alejandra Bosco and Monica L. Vetter§

University of Utah, Salt Lake City, UT

The image features nerve fibers (blue) and their attendant microglia (green), the cells responsible for immune defense in the central nervous system, as the fibers converge to form the optic nerve in a mouse retina. In glaucoma, the retina and optic nerve experience neurodegeneration that causes blindness. Researchers have discovered that mouse retinal microglia undergo changes preceding irreversible neuronal decline and death. Similar changes may take place in humans. By detecting and tracking the activity of microglia, researchers aim to identify and target early pathways underlying the onset of glaucoma. This research to further the development of more effective treatments to diagnose and slow glaucoma is supported by NIH funding from the National Eye Institute.

§Society for Developmental Biology

A. Kelsey Lewis1, Yong Wan1, Mary Colasanto1, Mark van Langeveld1, Ronen Schweitzer2§, Charles D. Hansen1, and Gabrielle Kardon1§

1University of Utah, Salt Lake City, UT

2Shriners Hospital, Portland, OR

Upper panel:

This is a limb from a transgenic, embryonic mouse, showing well established musculoskeletal and nervous systems. The limb is stained with a variety of techniques to differentiate muscle, tendon, bone, and nerve, and rendered into a three-dimensional image using FluoRender, a publicly available rendering program developed at the University of Utah.

Lower panel:

This is a model, derived from the upper panel image, showing muscles, tendons, bones, and nerves. This model is part of a collaborative effort between geneticists and computer scientists to develop a 3-dimensional interactive atlas of limb development. NIH funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development supports this effort.

§Society for Developmental Biology

Li-Hsien Lin†

University of Iowa

Both glutamate and nitric oxide play an important role in transmitting cardiovascular and respiratory signals between the brain, heart, and lung. This butterfly shaped figure is an image of a rat spinal cord showing the distribution of three types of glutamate and nitric oxide synthesizing enzymes. Understanding the action and interaction of glutamate and nitric oxide in the nervous system could lead to better treatments for cardiovascular diseases such as hypertension and heart failure. This work is supported by NIH funding from the National Heart, Lung and Blood Institute.

†American Physiological Society

Grigori Enikolopov and Ann-Shyn Chiang

1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY

2National Tsing Hua University, Taiwan

New neurons are produced from neural stem cells in several areas of the adult brain. One such area is in the hippocampus, a brain structure crucial for cognitive function. The number of neural stem cells in the hippocampus decreases over time, possibly contributing to the cognitive impairment associated with aging. When activated by extrinsic stimuli, stem cells divide and generate progenitor cells, which eventually mature into neurons and migrate into the layers above, whereas stem cells themselves undergo additional rounds of rapid divisions and convert into astrocytes, thus leaving the stem cell pool. The image depicts stem cells (green) and neuronal nuclei (red). This research to understand how the brain produces new neurons is supported by NIH through the National Institute of Mental Health and the National Institute of Aging.

Rakesh Karmacharya1, Stuart L. Schreiber2**, and Stephen J. Haggarty1

1Harvard Medical School, Boston, MA

2Harvard University, Cambridge, MA

The study of induced pluripotent stem (iPS) cell-derived neurons is a promising new approach to understanding the molecular and cellular underpinnings of schizophrenia, bipolar disorder, and other psychiatric diseases. Researchers are investigating the disease biology of psychiatric disorders by reprogramming patient skin cells to iPS cells and then generating live neuronal cells with the patients' genetic makeup. This image shows a culture of differentiated neuronal cells (green) and neural progenitor cells (red), with the nuclei of the cells in blue. This research is supported by NIH through the National Institute of Mental Health.

**American Society for Biochemistry & Molecular Biology