Page 26 - EUREKA! Summer 2018
P. 26

When Maria DeRosa and Matthew Holahan met,

                                                                                                                                     they saw that biochemistry and neuroscience
                                                                                                                                     could be combined with nanotechnology to

                                                                                                                                     advance the frontiers of health research.







             nybody who visits Carleton       To date, most PD treatments have   with nanotechnology to advance the
             chemistry professor Maria       focused on alleviating the disease’s   frontiers of health research, and they
        ADeRosa’s laboratory on the          symptoms, not its cause. But DeRosa   started working together in 2010,
        third floor of the university’s Steacie   and Holahan had another approach   investigating connections between
        Building will see a landscape of     in mind. “This project was science   dopamine and conditions such as
        labelled bottles, Styrofoam coolers,   fiction at the beginning,” says DeRosa.   schizophrenia and addiction.
        refrigerators and long black counters   “Finding the right aptamer was like   Dopamine, which plays a role in
        covered with beakers, computers and   looking for a needle in a haystack. But   both human pleasure and mobility, is
        microscopes. In one corner, dozens   we wanted to do something big.”     as essential to bodily movement as
        of thin plastic tubes fan out from    In November 2016, after sifting    motor oil is to an engine. Low levels
        a machine the size of a bar fridge,   through countless haystacks,       of the neurotransmitter are linked
        connecting amber bottles of clear,   DeRosa and graduate students Erin   to both addictive behaviour and
        purple and golden liquids to a nozzle   McConnell and Josh Callahan watched   neurodegenerative disorders such as
        inside a metal box. To an outsider, the   expectantly as their synthesizer   PD, which scientists believe may be
        lab may look cluttered, but it’s ground   made a new aptamer they had    tied to alpha-synuclein accumulation.
        zero for a meticulous research project   named A-syn-1. Two months later,   Together, DeRosa and Holahan had
        that has the potential to help spark a   test tubes containing A-syn-1 were   identified an aptamer that binds to
        medical breakthrough.                sent to Holahan’s lab, where he was   dopamine, but it proved difficult to
          In 2016, for nine months, that     conducting studies exploring levels of   target dopamine in the brain, and
        mechanical nozzle rhythmically       dopamine — a “chemical messenger”   they couldn’t secure the funding they
        whizzed and clicked as it squirted   that is responsible for transmitting   needed for exploratory studies, so
        droplets from the amber bottles into   signals within the brain — in mice that   they had to come up with a more
        rows of tiny test tubes. Those bottles   had been bred to develop PD-like   focused research project. “It didn’t
        contained a diverse set of reagents   symptoms such as slow movements,   help that this was something new, that
        — compounds that cause chemical      tremors and rigidity. These symptoms   we had an untested idea,” DeRosa
        reactions — which the machine, a     are associated with the clumping of a   says about shifting their investigation
        MerMade synthesizer, used to create   brain protein called alpha-synuclein.   to alpha-synuclein. “Most people
        billions of single-stranded DNA      Holahan and PhD student Katelyn     in neuroscience haven’t heard of
        molecules. Suspended in drops of     Ventura gave mice nine doses of     researchers using aptamers in this
        colourless liquid, these microscopic   A-syn-1 over three months, but before   way, so we couldn’t go to traditional
        strands of DNA are called aptamers,   they could even determine how      funding sources.”
        which bind to a variety of target    much of the aptamer had made it       It’s estimated that more than six
        molecules and have a long list of    into the rodents’ brains, they noticed   million people around the world are
        environmental, agricultural and health   something incredible. The amount of   affected by the mobility disorder
        applications.                        alpha-synuclein had been cut in half.  first characterized by English doctor
          DeRosa’s research group, the                                           James Parkinson 200 years ago. The
        Laboratory for Aptamer Discovery     After completing her PhD in         number of Canadians diagnosed with
        and Development of Emerging          chemistry at Carleton in 2003 and   PD is expected to exceed 164,000 by
        Research (LADDER), wants to develop   a postdoctoral fellowship at the   2031, according to Parkinson Canada.
        aptamers for use in fertilizers that   California Institute of Technology in   After epilepsy and Alzheimer’s
        seek out specific plants, for instance,   2004, DeRosa returned to Carleton as   disease, PD is responsible for the
        or to detect toxins in food and      a faculty member in 2005. Holahan,   third-highest healthcare costs in the
        airborne chemicals. And through a    who earned his master’s degree and   country, and the debilitating and
        series of collaborations with Carleton   PhD in psychology at Montreal’s   degenerative disease will only become
        Neuroscience professor Matthew       McGill University, arrived at Carleton   more prevalent and more expensive
        Holahan, she has also started        a year later. His research focused on   as baby boomers age. Parkinson’s
        hunting for aptamers that may help   memory, Alzheimer’s disease and     predominantly affects people who
        stop the second most common          neural development. When the two    are older than 60, although about 10
        neurodegenerative brain disorder:    met, they saw that biochemistry and   percent of people with PD are younger
        Parkinson’s disease (PD).            neuroscience could be combined      than 50, and it can start at a much



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