Distribution of skeletal proteins in an artificial membrane resembling a long bacteria: The spontaneous curvature of the proteins (purple) drives them to move together to form rings that coalesce, increasingly constricting the membrane

A doctoral student with a degree in physics, who conducts research on biological systems in the Faculty of Chemistry, has received an award given by the Faculty of Mathematics. To Roie Shlomovitz, a student in the group of Prof. Nir Gov of the Chemical Physics Department and the 2010 recipient of the Lee A. Segel Memorial Prize in Theoretical Biology, this makes perfect sense. Prof. Segel, a member of the Weizmann Institute’s Mathematics and Computer Science Faculty for many years who passed away in 2005, was one of the first to cross the boundaries between the disciplines of mathematics and the life sciences, showing that mathematics could be used to describe the dynamics of biological systems and teaching biologists to think “mathematically.” “My work fits right in with Segel’s approach,” says Shlomovitz.

Shlomovitz and Gov investigate proteins that form the cell’s internal skeleton. These proteins – actin and myosin – make up the fibers that enable our muscles to contract and are involved in cell movement and cell division. When a cell moves, actin filaments gather on the leading side, forming a bulge that propels the cell onward. In cell division, actin and myosin proteins create a ring encircling the cell’s midriff, squeezing the membrane tightly and pinching it in two.

What causes these proteins to push the cell membrane outward in one case and constrict it in another? How do they “know” when and where to apply pressure? To address such questions, Shlomovitz and Gov observe what happens to these proteins in cells, turn the data into mathematical models and, finally, test the predictions of their models in such biological systems as yeast. According to their model, actin and myosin proteins get their directions from the shapes of molecules in the cell’s membrane. When the cell is about to move, the membrane points the way by exaggerating its outward curve on one side. The convex membrane molecules “invite” the actin to gather round; large amounts of these molecules and the actin flock to the site to drive the edge forward. In the early stages of cell division, on the other hand, the membrane’s center takes on an inward curve. Investigating bacterial proteins, the researchers found that concave curves attract these proteins, as well: A circular network of actin and myosin marks the division line.

The mathematical model they developed borrowed an equation from physics that describes the free energy of a system. Using this equation, they calculated the distribution of proteins in the membrane and revealed how this distribution relies on the membrane’s shape. The researchers showed exactly how the bowed segment induces the proteins to encircle the membrane right at the center, how the growing inward bend of the membrane continuously attracts more proteins to the spot to increase the constriction, and how the distance between one protein and the next determines whether they’ll become a part of the tightening band or form separate rings.

Their model not only predicted the behavior of these proteins on artificial membrane bulges and indents; an experimental group in Taiwan found it could also explain the wavy shapes of living cell membranes. Shlomovitz: “We describe the complex biological processes occurring within a single cell by constructing chemical and physical models. Mathematics is the ‘language’ we use to analyze them.”

Prof. Nir Gov’s research is supported by the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly.

(l-r) Dr. Asaph Aharoni, Dr. Ilana Rogachev, Tal Mendel and Dr. Avital Adato. More than a pretty color

Aharoni’s lab has a system that’s unique in Israel, and one of only a few in the world. Using a combination of molecular, chemical and analytical methods, he and his research team are able to identify hundreds of metabolites – active compounds in plants – and create a comprehensive profile of all the substances produced in the mutant plant, which is then compared with that of normal plants.

The scientists found that the difference between pink and red tomatoes goes much deeper than an absence of yellow pigment in the skin: They identified around 400 genes whose activities were radically different in the mutants – at least twice as intense or less than half of normal. The mutation influenced the production of a number of substances in the flavonoid family, both in the cuticle and in the flesh of the fruit. In addition, pink tomatoes contain less lycopene – a red pigment and powerful antioxidant known to have a number of health benefits. The pink cuticle is thinner than the red one but less flexible, due to alterations in the composition of the fatty substances.

The gene mutated in the pink tomato, known as SIMYB12, is a sort of “master switch” that regulates an entire network of other genes, overseeing the production and quantities of many metabolites in the tomato fruit. Aharoni: “Researchers can now use this gene as a ‘marker’ to reveal the future color of the fruit early on – months before the plant flowers and bears fruit. This might greatly accelerate the creation of new varieties, a process that normally can take 10 years or more.”
 

Dr. Asaph Aharoni’s research is supported by the De Benedetti Foundation-Cherasco 1547; and the Willner Family Foundation. Dr. Aharoni is the incumbent of the Adolpho and Evelyn Blum Career Development Chair of Cancer Research.

Dr. Arieh Moussaieff

Color It Mellow

 

The rabbis who wrote the Talmud around 1,500 years ago knew about the unique properties of frankincense (levona in Hebrew). They sanctioned adding a pinch of the aromatic tree resin to the wine of a condemned criminal, to “benumb his senses.” Research by Dr. Arieh Moussaieff, a postdoctoral fellow in Dr. Asaph Aharoni’s lab, shows that this resin, gathered for thousands of years from trees of the genus Boswellia, contains compounds that relieve depression and anxiety.

 

Moussaieff first encountered frankincense while researching a plant-based remedy made in a monastery in Jerusalem’s Old City. In folk medicine, the resin is believed to have anti-inflammatory properties, and to ease digestive and respiratory problems. But frankincense is most widely used as incense in religious ceremonies ranging from ancient Egyptian, Jewish and Christian rites to Chinese and Indian rituals.

 

In his doctoral work at the Hebrew University of Jerusalem, Moussaieff isolated the active compounds in the resin. When tested on mouse models of human head injury, he found that some of these substances provide protection for the nervous system. He later noted the resin’s antidepression and antianxiety properties and, investigating further, found that they act on a previously unknown pathway in the brain that regulates emotion. These findings not only help explain the ubiquity of frankincense in religion, they also hint that the active compounds might be used in the future to treat any number of neurological diseases, from Alzheimer’s and Parkinson’s to depression.

 

Moussaieff’s current research involves investigating how the resin is produced in the tree. The active compounds are, at present, too complex to manufacture on a marketable scale, and he hopes that uncovering the natural mechanisms of frankincense creation in the tree will point the way toward methods of producing it efficiently.