Max Planck Florida researcher Samuel M. Young, Jr., PhD has received his first grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF). The grant will enable Dr. Young and colleagues to develop a technology to assist scientists working in drug development to research potential treatments that target LRRK2, a Parkinson’s-related gene. Globally, five million people have Parkinson’s disease.
“We are excited about receiving The Michael J. Fox Foundation grant, as these grants are competitive and MJFF is the world’s largest private funder of Parkinson’s research,” said Dr. Young, who directs MPFI’s Molecular Mechanisms of Synaptic Function research group. “We believe that the tools we develop will prove important in advancing Parkinson’s research.”
Translational researchers working in Parkinson’s disease have been hindered in studying the function of the LRRK2 gene in pre-clinical models of Parkinson’s. This has been due to difficulty in expressing this gene with commonly used neuroscience research tools known as recombinant viral vectors. Dr. Young will develop tools that will allow researchers to get around this problem.
Mutations in the gene for leucine-rich repeat kinase 2 (LRRK2) are among the most common genetic links to Parkinson’s disease yet discovered. LRRK2 has garnered much excitement among drug makers due to its reported protein kinase activity, which appears to be enhanced by Parkinson’s disease-causing mutations.
“We are delighted that The Michael J. Fox Foundation has awarded Dr. Young with a grant to lead this critical project,” said David Fitzpatrick, PhD, CEO and Scientific Director of MPFI. “This grant recognizes Dr. Young’s specialized expertise, as well as our Institute’s leadership role in neural circuit research.”
Recombinant viral vectors are used by scientists to deliver genetic material into cells. Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect. To create the vector, viruses are bioengineered to strip their viral genome or most of their viral genome, which renders them harmless. This enables them to carry transgene expression cassettes to express a gene of interest. The transgene expression cassette is a fragment of DNA that carries the regulatory elements necessary for cells to express specific genes within a cell or organism.
As the principal investigator of the project, Dr. Young will work with collaborators at other institutions to generate the optimal expression cassette to express LRRK2.
Dr. Young has specialized training that makes him the ideal investigator for this project. After training in virology and in recombinant viral vectors during his doctoral studies, Dr. Young switched fields and became a post-doctoral neuroscience researcher, learning electrophysiology techniques. He carried out a second post-doctoral position, gaining further experience with advanced electrophysiological techniques as well as calcium imaging. Using this unique training, which combines techniques in molecular, electrophysiological and biophysical methods, Dr. Young and his group at MPFI study the molecular mechanisms regulating synaptic function. Understanding these mechanisms is critical because the major causes of brain diseases are due to synaptic dysfunction.
Since Dr. Young’s arrival at MPFI in 2010, he and his team have made significant progress in their research. After finding that most transgene expression cassettes were not optimized for high level expression for use in neuroscience research, the team, including Dr. Monica Montesinos and graduate student Zuxin Chen, developed and published a research manuscript describing a novel expression cassette known as “pUNISHER” for neuroscience applications. The cassette, which can be used inside a living organism (in vivo) or in cell culture (in vitro), has the potential to help the research of scientists studying the molecular mechanisms of brain function, and to ultimately be used in translational research on disorders such as Parkinson’s, Huntington’s and Alzheimer’s diseases.