[Steve Frey]

The Ancestor’s Tale
Sponge research focuses on drug discovery and the origins of multicellularity
by Martin Colaco

To the average agent of kitchen cleanliness, the sponge does not evoke particularly strong feelings. However, the marine filter feeder of the same name—now only a spiritual cousin of the yellow and green dish-scrubbing staple—has been stirring the imaginations of biologists and engineers for a number of reasons. Though among the simplest of multicellular organisms, sponges produce a variety of molecules with anticancer, antiviral, and anti-inflammatory properties. Current research at UC Berkeley investigates the biology of sponges to understand their evolution and to learn how to manufacture their natural products.

In the 1950s, a number of previously unknown pharmaceutical products were discovered in sponges. Most of the compounds are produced in very low amounts, so harvesting the sponges from the wild to extract these compounds is impractical at best. However, these molecules are so complex that synthesizing them chemically is currently unachievable. Thus, learning how to grow sponges in a laboratory environment is critical to producing these chemicals in usable quantities. Sponges can grow under diverse conditions, thriving in fresh and salt water, in polar and tropical regions, and in deep seas and shallow waters; however, attempts to grow them in the lab, whether cultured as individual cells or as whole sponges, have been unsuccessful.

Detmer Sipkema, a postdoctoral fellow in Harvey Blanch’s lab in the chemical engineering department, has been working on this problem for four years. His research initially focused on culturing sponge cells, but he now works on growing sponge-associated bacteria. This is because it is not clear whether the valuable chemicals found in sponges are produced by the sponge cells themselves or by the sponges’ bacterial symbionts. Analyzing the DNA of samples from the sponge Haliclona (Gellius) sp., Sipkema was able to isolate 15 types of associated bacteria and has successfully cultured two of them. To culture the other 13 types, he is trying to “mimic certain microenvironments of the sponge to seduce them to grow.” For example, bacteria associated with the outer layers of the sponge might require light for optimal growth, while bacteria that live in the sponge’s center might prefer the dark. By providing the right environment for each type of bacterium, Sipkema believes that he can disprove the commonly held notion that “only one percent of bacteria from…sponges can be cultured.”

While Sipkema’s interest in sponges focuses on culturing individual sponge cells and the bacteria that associate with them, Scott Nichols, a postdoctoral fellow in Nicole King’s lab in the molecular and cell biology department, wants to understand how animals develop and evolve. To this end, sponges are of particular interest. They are among the simplest multicellular animals, and some of their cells are very similar to choanoflagellates, which are the closest living unicellular relative of animals [see “United We Stand”, BSR Spring 2006]. In addition, there is mounting evidence that all multicellular animals evolved from a sponge-like ancestor. Examining the traits that sponges share with animals but not with choanoflagellates could help reveal which traits developed first, and thus may be most important, in the evolution of more complex organisms.

“To develop multicellularity,” says Nichols, “[organisms] need cell communication and cell adhesion.” Other researchers have determined that a protein called beta-catenin is involved in both of these processes in more complex animals such as fruit flies and mice. In the presence of an external signal, beta-catenin helps regulate gene expression in the cell nucleus. This signaling pathway is critical to animal health, and its breakdown has been linked to cancer growth. Beta-catenin also serves a role in cell adhesion: Without it, a protein that attaches cells to one another cannot function.

Little is known about the mechanism of cell adhesion and signaling in sponges. Nichols recently discovered the beta-catenin gene in the sponge Oscarella carmela. In addition, he identified a number of other genes that are involved in cell adhesion or signaling in higher animals—for example, genes that are used in limb and tissue formation. Why sponges have these genes when they do not exhibit the body diversification of other animals is unclear, but Nichols’s early research indicates that beta-catenin is used for both cell signaling and cell adhesion in sponges. Confirmation of this hypothesis is difficult, Nichols says, because the molecular tools required to study gene expression and regulation have not been established for sponges as they have for other organisms.

Both Sipkema’s and Nichols’s research point to a fundamental limitation in sponge research: the lack of a model organism. Currently, there is no species of sponge that is readily available, easy to grow and work with, and to which modern techniques in biology can be applied. To date, most researchers have chosen to study sponge species based on whatever was most abundant in the wild, since they could not grow sponges in the lab. But both Sipkema and Nichols believe that, with enough researchers and time, it should be possible to culture sponge cells and their associated bacteria. A model sponge might give us a better understanding of how multicellular life began to develop in the past and at the same time provide us with the life-saving medications of the future.

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