Monday, 23 June 2008

Weekly BioNews 16 - 23 June 2008

- Ability to track stem cells in tumors could advance cancer treatments

June 16, 2008 06:34 PM

Using noninvasive molecular imaging technology, a method has been developed to track the location and activity of mesenchymal stem cells (MSCs) in the tumors of living organisms, according to researchers at SNM's 55th Annual Meeting. This ability could lead to major advances in the use of stem cell therapies to treat cancer.

"Stem cell cancer therapies are still in the early stages of development, but they offer great promise in delivering personalized medicine that will fight disease at the cellular level," said Hui Wang, a postdoctoral fellow from Prof. Xiaoyuan (Shawn) Chen's group of the Molecular Imaging Program at Stanford (MIPS), Department of Radiology at Stanford University, Stanford, Calif., and lead researcher of the study, Trafficking the Fate of Mesenchymal Stem Cells In Vivo. "Our results indicate that molecular imaging can play a critical role in understanding and improving the process of how stem cells migrate to cancer cells. Eventually, this technique could also be used to determine if gene-modified stem cells are effective in fighting cancer."

MSCs are adult stem cells that have the ability to transform into many different types of cells, such as bone, fat or cartilage. Many scientists believe that stem cells show great promise in treating different types of diseases—and a few stem cell therapies are already used to fight some types of cancer. Leukemia patients who haven't responded to chemotherapy, for example, may receive bone marrow transplants, through which stem cells of a healthy bone marrow donor are injected into the patient's blood stream. If the transplant is successful, the stem cells will migrate to the patient's bone marrow and begin producing healthy cells that will replace the cancer cells. For other types of cancer, researchers are experimenting with modifying stem cells that could be engineered to deliver chemotherapy more precisely to specific tumor sites.

For these types of treatments to be successful, the ability to track what happens to stem cells after they are injected into a living organism is essential. Currently, three different tracking techniques are used: radiolabeling, which consists of using a radioactive substance to tag the cells; magnetic labeling, or using magnetic nanoparticles to tag cells for magnetic resonance imaging; and reporter-gene tracking, which involves engineering genes that can adhere to cells and be tracked with molecular imaging technologies. Of these, reporter gene techniques are highly sensitive and able to monitor cell migration, survival and proliferation over time in living organisms....

- Could New Discovery About A Shape-shifting Protein Lead To A Mighty 'Morpheein' Bacteria Fighter?

ScienceDaily (June 20, 2008)

A small molecule that locks an essential enzyme in an inactive form could one day form the basis of a new class of unbeatable, species-specific antibiotics, according to researchers at Fox Chase Cancer Center.

Their findings, highlighted on the cover of the June 23 issue of the journal Chemistry & Biology, take advantage of an emerging body of science regarding "morpheeins" -- proteins made from individual components that are capable of spontaneously reconfiguring themselves into different shapes within living cells.

The researchers discovered a small molecule, which they have named morphlock-1, binds the inactive form of a protein known as porphobilinogen synthase (PBGS), an enzyme used by nearly all forms of cellular life. The functioning form of PBGS is built from eight identical component parts -- in what is called an octamer configuration -- and is essential among nearly all forms of life in the processes that enable cells to use energy. The other configuration is made of six parts -- or a hexamer configuration -- and serves as a "standby" mode for the protein.

"As the name suggests, morphlock-1 essentially locks the hexamer configuration into place, preventing its protein subunits from reconfiguring into the active assembly," says lead investigator Eileen Jaffe, Ph.D, a Senior Member of Fox Chase. "Targeting morpheeins in their inactive assemblies provides an entirely new approach to drug discovery."

While their study was performed using a pea plant-version of PBGS, the researchers have reason to believe the principle could apply to bacterial versions of PBGS as well. "Using morphlock-1 as a base, we are seeking to fine tune the molecule so that it blocks just the bacterial version of the PBGS enzyme, " Jaffe says....

Morphlock-1 (yellow) binds the inactive form of a protein known as PBGS, an enzyme used by nearly all living things. The functioning form of PBGS is built from eight identical component parts, in what is called an octamer configuration (pink). The hexamer configuration (blue) is made of six parts. (Credit: FCCC)

- Toward Designing Medications To Enhance Innate Immunity: A Single VSOP Can Do 'Proton' Magic

ScienceDaily (June 20, 2008)

International research group led by Yasushi Okamura, a professor in Japanese National Institute for Physiological Sciences, Okazaki, and Peter Larsson, a professor in Oregon Health & Science University, Oregon, US, found that a single protein of VSOP, Voltage Sensor Only Protein/ Hv1, can carry protons even without making a multimeric complex.

Since VSOP is known to be expressed in phagocytes such as macrophages and neutrophils that remove infected pathogens, this finding may help in the design of new medications for enhancing the activities of innate immunity.

Usually, ion channels on cell membrane form a multimeric complex to make an assembling hole to carry ions though. Surprisingly, the research group found that this VSOP protein forms a dimer but each single subunit can carry protons without any assembling hole. They reached these conclusions through using the techniques of FRET (Fluorescence Resonance Energy Transfer) and biochemistry.

The VSOP keeps the cell inside in an alkaline condition. This finding helps to explain how VSOP regulates pH conditions during the process of removing pathogens such as fungi, bacteria and virus.

VSOP/Hv (middle) usually forms a dimer but each subunit can carry protons without making any assembling hole. (Credit: Copyright Yasuhi Okamura)
- Zebra's Stripes, Butterfly's Wings: How Do Biological Patterns Emerge?

ScienceDaily (June 20, 2008)

A zebra’s stripes, a seashell’s spirals, a butterfly’s wings: these are all examples of patterns in nature. The formation of patterns is a puzzle for mathematicians and biologists alike. How does the delicate design of a butterfly’s wings come from a single fertilized egg? How does pattern emerge out of no pattern?

Using computer models and live cells, researchers at Johns Hopkins have discovered a specific pattern that can direct cell movement and may help us understand how metastatic cancer cells move.

“Pattern formation is a classic problem in embryology,” says Denise Montell, Ph.D., a professor of biological chemistry at Hopkins. “At some point, cells in an embryo must separate into those that will become heart cells, liver cells, blood cells and so on. Although this has been studied for years, there is still a lot we don’t understand.”

As an example of pattern formation, the researchers studied the process of how about six cells in the fruit fly distinguish themselves from neighboring cells and move from one location in the ovary to another during egg development. “In order for this cell migration to happen, you have to have cells that go and cells that stay,” says Montell. “There must be a clear distinction — a separation between different types of cells, which on the surface look the same.”

A zebra's stripes, a seashell's spirals, a butterfly's wings: these are all examples of patterns in nature. The formation of patterns is a puzzle for mathematicians and biologists alike. How does the delicate design of a butterfly's wings come from a single fertilized egg? How does pattern emerge out of no pattern? (Credit: iStockphoto/Ismael Montero Verdu)

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