Mother nature to the rescue

May 1, 2012, Weizmann Institute of Science

(Medical Xpress) -- Natural molecules that protect the body against disease are finding their way into the treatment of advanced cancer. Prof. Michel Revel of the Department of Molecular Genetics has played a leading role in the discovery and study of two natural molecules now employed as drugs. In the late 1970s, Prof. Revel isolated the gene for interferon-beta, a human protein that fights viral infection in the body and is used as a drug against a variety of ills, including certain types of cancer—particularly glioma and non-small-cell lung carcinoma.

Another important molecule isolated in Prof. Revel’s lab is interleukin-6, or IL-6, an immune system protein involved in defending the body against infection and inflammation. Because this protein boosts the production of blood platelets, it can offset the loss of blood cells that often accompanies intensive forms of traditional cancer therapies—chemotherapy or radiation. IL-6 may also improve blood cell formation after bone marrow transplantation.

Moreover, IL-6 can play a role in cancer treatment itself. One possibility being tested in clinical trials is to use IL-6 to improve the effectiveness of vaccines against advanced cancer such as melanoma. Studies conducted by Prof. Revel, along with the Weizmann Institute’s Prof. Lea Eisenbach, revealed that IL-6 prevents the development of metastases in animals, probably through the same immune mechanisms as those at work in vaccines. In another promising research direction, Prof. Revel’s team created an IL-6 “chimera”—a recombinant molecule that boosts IL-6’s therapeutic potential. In animal tissue, the chimera, consisting of IL-6 and its receptor fused together, has been shown to block a protein important for the survival of melanoma cells. The Weizmann scientists have started collaborating with Italian researchers to investigate the effects of the IL-6 chimera on human melanoma tumors. In addition, in collaborative research with the Institute’s Prof. Tsvee Lapidot, the IL-6 chimera molecule was found to improve the success of blood stem cell transplantation.

Interferons—natural anti-viral proteins—have been approved as drugs for treating viral diseases and various . However, their use is limited by undesirable side effects; moreover, cells sometimes develop resistance to interferons or release antibodies to neutralize the drugs. These limitations may be overcome if scientists achieve a molecular understanding of how interferons bind to their cellular receptor. The laboratory of Prof. Jacob Anglister of Weizmann’s Department of Structural Biology is aiming to elucidate the three-dimensional (3D) structure of the outer part of the interferon receptor, the part that protrudes beyond the cell membrane. The scientists are also studying the complex formed by the receptor with one particular interferon—interferon-alpha2. This research is conducted using nuclear magnetic resonance (NMR) spectroscopy, a powerful tool for studying the 3D structure of proteins. The structural information gained from this study is expected to pave the way for the design of interferons and interferon-like molecules with greater therapeutic results and fewer harmful side effects.

Using different technologies, Prof. Gideon Schreiber of the Department of Biological Chemistry studies the complexes formed by interferons and their receptors. Prof. Schreiber focuses on an important puzzle in the field: how is it that interferons alpha and beta bind to the same receptors on the cell membrane but produce different effects inside the cell, turning on different genes at varying intensities? Because standard methodologies have failed to produce an adequate image of the complexes’ structure, Prof. Schreiber’s team developed a new strategy. Their approach is to experimentally identify points of “docking” between the two proteins and incorporate these points into a so-called docking algorithm, a computer program that creates a 3D image of the complex. The docking points are identified using a sophisticated method, double mutant cycling, which systematically introduces mutations into the amino acids making up the protein in order to study this protein in great detail. Understanding the details of the complex interactions between different interferons and their receptors promises to provide means for designing improved interferons to fight disease.

Explore further: Cracking the interferon code

Related Stories

Cracking the interferon code

August 24, 2011
(Medical Xpress) -- Interferons, protective chemicals produced by most cells in the body, live up to their name, hampering cancer and viral infections. It takes many different kinds of interferon molecules to get the job ...

Genetic diversity: Crucial for our survival in many ways

December 20, 2011
(Medical Xpress) -- Thanks to the sequencing of the 27 known human interferon genes, researchers from the Institut Pasteur and the CNRS reconstruct the genetic history of these proteins so central for our immune system, and ...

Metastatic breast cancer hitches a free ride from the immune system

February 10, 2012
Inflammatory breast cancer (IBC) is the most lethal form of breast cancer . It spreads easily through the lymphatic and blood vessels, forming metastasis which can lead to multi-organ failure. New research published in BioMed ...

Recommended for you

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

Researchers devise decoy molecule to block pain where it starts

January 16, 2018
For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.

Scientists unleash power of genetic data to identify disease risk

January 16, 2018
Massive banks of genetic information are being harnessed to shed new light on modifiable health risks that underlie common diseases.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.