I’m going to stick my neck out a bit here, and discuss some chemical biology, even though I wouldn’t claim to be much of a biology expert. Apologies if some of the details are a bit ropy.

This morning, Linda Hsieh-Wilson gave an inspiring talk on her work unravelling the role of the polysaccharide chondroitin sulfate (CS) in modulating neuron growth. Naturally occurring CS is a mixture of compounds, each containing a different pattern of sulfate groups. This makes it difficult to tease out the effects of particular sulfation patterns, but Hsieh-Wilson’s group have made several tetrasaccharides as models of CS, each with one of the different characteristic arrangements of sulfates found in the parent molecule.

They find that only one of these tetrasaccharides (called CS-E) promotes neuron growth in their in vitro studies. Using CS-E as a molecular probe, they’ve now started to unravel the likely biological mechanism of action. It seems that CS-E forms a ternary complex with brain-derived neurotrophic factor and the receptor TrkB. Blocking formation of this complex prevents CS-E-mediated neurite growth.

But CS is a double-edged sword – it can also prevent neuron regeneration after injury. Hsieh-Wilson is now using her compounds to unpick the reasons for this. Her tetrasaccharides weren’t effective substitutes for CS in in vitro models of neuron regeneration, so her team came up with a method to prepare CS-E polymers (containing 25-80 sugar units). Sure enough, these polymers inhibit neuron regeneration, showing that the CS-E sulfation pattern is most likely responsible for the biological effect. Furthermore, an antibody that blocks CS-E activity was able to counteract the inhibition, thus encouraging neuron repair.

Exciting stuff, especially as there is currently no way to stimulate regeneration of damaged neurons. Of course, this is a long way off providing anything that would be therapeutically useful, but just being able to unpick the biological mechanisms that prevent neuron regeneration strikes me as being incredibly useful. And it’s a perfect example of how chemistry can provide tools that answer biological questions.

Andy

Andrew Mitchinson (Senior Editor, Nature)

Posted for Emma Marris

The Ecological Society of America annual meeting begins today in Milwaukee, Wisconsin. Milwaukee is best known for beer brewing, Harley Davidson motorcycles and its rust-belt decline. I decided to skip the whole question of Milwaukee as a city and examine Milwaukee as an ecosystem. I began by joining a field trip that visited a forest and a prairie, both remnants of ecosystems that once covered the area in a fluctuating mosaic controlled by fire.

The prairie, a sea of grasses, sedges, flowers and reeds, blooms from the earth after a fire from a seed bank that contains, in the case of Chiwaukee prairie, over 400 plant species. Bison would have grazed in such places. Today, the Department of Natural Resources struggles to keep this ecosystem from growing bushy. Burning is “tricky”, according to Marty Johnson of the Wisconsin Department of Natural Resources, as there are many houses adjacent to the prairie. The state is attempting to buy up these residential lots (developers named the area “Pleasant Prairie”) to expand the habitat. He crew spends its time yanking out invasive species year-round. “Whatever is blooming, you deal with,” he says. The prairie comes up to my shoulder in some places, and is at the moment alive with purple and yellow blooms. As I swished through the grass, I smelled wild bergamot and mountain mint.

Meanwhile, Renak-Polak Woods is a remnant of maple-beech forest, the ecosystem type that typically grew up in the absence of fire. The forest persisted because of two landowners that chose not to develop it for the pleasingly uneconomic reason that they liked it. Sugar maple and smooth-barked beech—"like an elephant’s leg," according to Joy Wolf, a geographer at the University of Wisconsin Parkside—give the forest its name. Black cherry, many-trunked beech, and small herbaceous plants like bloodroot, wild ginger and red baneberry share the woods. Ephemeral ponds come and go, and we found a salamander and a number of crawfish nests to testify to their inhabitants.

These fragments are examples of what the landscape looked like when European settlers arrived. The difference, of course, is that these patches are held static in one phase—prairie or maple-beech forest—whereas the pre-settlement landscape was in reality a shifting mosaic of these and other types mediated by fires, fires often set by the Native Americans. So, in essence, these beautiful repositories of biodiversity are like fine museum pieces displaying fragments of an earlier, and perhaps more successful, land management philosophy for the Milwaukee area.