The language of neural cells

Heather Clark, an asso­ciate pro­fessor of phar­ma­ceu­tical sci­ences at North­eastern Uni­ver­sity, has received a $300,000 Young Fac­ulty Award from the Defense Advanced Research Projects Agency to explore neural cell com­mu­ni­ca­tion using her exper­tise in nanosensors.

"We were inter­ested in looking into neural cells because of the need to mea­sure chem­i­cals in the brain," she explained.

In sep­a­rate work, Clark had already been devel­oping nanosen­sors to mea­sure the bio­chem­ical envi­ron­ment inside a single neuron. The DARPA award will allow her team to extend the inves­ti­ga­tion to the bio­chem­ical reac­tions between cells. "We will use the chem­istry devel­oped for another DARPA project and apply it to making a sensor for neu­ro­trans­mitter release," Clark said.

The other DARPA project, she noted, enabled the team to incor­po­rate enzymes into their sensor format. Post­doc­toral researcher Kevin Cash did the bulk of this work, devel­oping sen­sors that mon­itor the byprod­ucts of enzy­matic reactions.

As Clark put it, "We can mea­sure a whole lot more mol­e­cules that way."

When a neural cell sends a mes­sage to another cell, it releases mol­e­cules into the inter­cel­lular envi­ron­ment. The new nanosensor will incor­po­rate an enzyme that reacts with these mol­e­cules to pro­duce acidity changes. A pH mon­itor also incor­po­rated into the nanosensor will rec­og­nize those acidity changes and pro­duce a signal equiv­a­lent to the con­cen­tra­tion of the neurotransmitter.

This indi­rect mea­sure­ment process will allow Clark's team to mea­sure neu­ro­trans­mitter levels without directly binding to them, a chal­lenge in its own right. "But enzymes do a really great job of rec­og­nizing [these mol­e­cules] nat­u­rally," said Clark. "It's what they do best."

The researchers have devel­oped other sen­sors that use this same chem­ical pro­tocol, but the dif­fi­culty lies in get­ting them into the inter­cel­lular space. "We're not actu­ally working in the whole brain, we're working in slices [of the mouse brain]," Clark explained. "So we're hoping to just flush it into the tissue layer."

Col­lab­o­ra­tors at Har­vard Med­ical School will apply their exper­tise in keeping brain tissue alive in solu­tion for these types of tests. But before reaching that level of inves­ti­ga­tion, the North­eastern researchers will val­i­date the nanosen­sors in in vitro and model cel­lular settings.

In addi­tion to receiving funding, YFA awardees are paired with DARPA pro­gram man­agers who share sim­ilar inter­ests. Clark's mentor is a med­ical doctor with exper­tise in microscale and nanoscale bio­med­ical tech­nolo­gies. "It's always my goal to do some­thing that is med­ically and clin­i­cally rel­e­vant," Clark said. "I think that will be good insight."

Provided by Northeastern University