April 27, 2018
Abstract: The transition from non-dependent alcohol use to alcohol dependence involves increased activity of the dorsal striatum. Interestingly, the dorsal striatum expresses a large number of inhibitory G-protein-coupled receptors (GPCRs), which when activated may inhibit alcohol-induced increased activity and can decrease alcohol consumption. Here, we explore the hypothesis that dorsal striatal Gi/o-protein activation is sufficient to reduce voluntary alcohol intake. Using a voluntary, limited-access, two-bottle choice, drink-in-the-dark model of alcohol (10%) consumption, we validated the importance of Gi/o signaling in this region by locally expressing neuron-specific, adeno-associated-virus encoded Gi/o-coupled muscarinic M4 designer receptors exclusively activated by designer drugs (DREADD) in the dorsal striatum and observed a decrease in alcohol intake upon DREADD activation. We validated our findings by activating Gi/o-coupled delta-opioid receptors (DORs), which are natively expressed in the dorsal striatum, using either a G-protein biased agonist or a ?-arrestin-biased agonist. Local infusion of TAN-67, an in vitro-determined Gi/o-protein biased DOR agonist, decreased voluntary alcohol intake in wild-type and ?-arrestin-2 knockout (KO) mice. SNC80, a ?-arrestin-2 biased DOR agonist, increased alcohol intake in wild-type mice; however, SNC80 decreased alcohol intake in ?-arrestin-2 KO mice, thus resulting in a behavioral outcome generally observed for Gi/o-biased agonists and suggesting that ?-arrestin recruitment is required for SNC80-increased alcohol intake. Overall, these results suggest that activation Gi/o-coupled GPCRs expressed in the dorsal striatum, such as the DOR, by G-protein biased agonists may be a potential strategy to decrease voluntary alcohol consumption and ?-arrestin recruitment is to be avoided.
Critical Role for Gi/o-Protein Activity in the Dorsal Striatum in the Reduction of Voluntary Alcohol Intake in C57Bl/6 Mice- Dr. Richard M. van Rijn
April 27, 2018
Abstract: To attenuate an overabundance of cellular protein, it has been hypothesized that the 20S core particle (20S CP) of the proteasome can be chemically stimulated to degrade proteins into nontoxic peptides more quickly. Screening for small molecule 20S CP stimulators is typically performed with a reporter peptide composed of four amino acids and a coumarin group that is released upon proteasome-mediated hydrolysis to generate a fluorescent signal. Screening with this small reporter can lead to false negatives because the reporter peptide is rapidly turned-over without stimulation. To improve the screening for 20S CP stimulators, we have developed a peptide FRET reporter nearly four times more sensitive to stimulation but still amenable for high throughput screening. Through the application of our FRET reporter, we have discovered two 20S CP gate-opening stimulators and also a molecule that elicits its mechanism of action through an interaction with a 20S CP active site.
Development and Application of a Sensitive Peptide Reporter to Discover 20S Proteasome Stimulators- Dr. Darci J. Trader
April 24, 2018
Julia A. Chester, Ph.D. Associate Professor Department of Psychological Sciences, won the Jane S. Link College of Health and Human Sciences Teaching Award.
April 24, 2018
The Purdue Chapter of Sigma Xi, the Scientific Research Honor Society for scientists and engineers awarded Professor Jennifer L. Freeman ( Associate Professor of Toxicology) with the newer Mid-Career Research Award.
Professor Jennifer L. Freeman was awarded the newer Mid-Career Research Award
April 24, 2018
Professor Stephen Konieczny (Biological Sciences) was recognized as this year's winner of the Sigma Xi Research Award. This award began in 1950 and Dr. Konieczny is the 66th recipient.
Professor Stephen Konieczny was recognized as this year's winner of the Sigma Xi Research Award
April 20, 2018
Two members of the Purdue Institute for Integrative Neuroscience, Dr. Chris Rochet, and Dr. Riyi Shi recently discover a key factor in the development of Parkinson’s disease that could lead to new therapies, potentially including drugs currently on the market. This discovery could facilitate earlier diagnosis and prevention of the neurological disorder.
'Key factor' in development of Parkinson's disease identified- Dr. Chris Rochet and Dr. Riyi Shi
April 20, 2018
For the educational component of the NSF CAREER award, Tamara Kinzer-Ursem, an assistant professor of biomedical engineering, will develop a new educational pathway to prepare Weldon School students for careers in biotechnology and biomedical engineering.
April 20, 2018
Advancements in microfabrication has enabled manufacturing of microscopic neurostimulation electrodes with smaller footprint than ever possible. The smaller electrodes can potentially reduce tissue damage and allow better spatial resolution for neural stimulation. Although electrodes of any shape can easily be fabricated, substantial effort have been focused on identification and characterization of new materials and surface morphology for efficient charge injection, while maintaining simple circular or rectangular Euclidean electrode geometries. In this work we provide a systematic electrochemical evaluation of charge injection capacities of serpentine and fractal-shaped platinum microelectrodes and compare their performance with traditional circular microelectrodes. Our findings indicate that the increase in electrode perimeter leads to an increase in maximum charge injection capacity. Furthermore, we found that the electrode geometry can have even more significant impact on electrode performance than having a larger perimeter for a given surface area. The fractal shaped microelectrodes, despite having smaller perimeter than other designs, demonstrated superior charge injection capacity. Our results suggest that electrode design can significantly affect both Faradaic and non-Faradaic electrochemical processes, which may be optimized to enable a more energy efficient design for neurostimulation.
Electrode shape improves neurostimulation for small targets- Dr. Hugh Lee
April 5, 2018
As part of its Integrative Data Science Initiative, Purdue is launching an internal funding opportunity for ambitious proposals that apply data science to pressing, socially relevant issues. The funding will leverage the University's existing strengths in data analytics to help position Purdue as a leader in science-enabled research, says Tomás Díaz de la Rubia, chief scientist and executive director of Discovery Park, who is spearheading the research thrust of the initiative.
Discovery Park announces request for proposals to support data science initiative
April 5, 2018
As part of its Integrative Data Science Initiative, Purdue is launching an internal funding opportunity for ambitious proposals that will expand data science education across campus. Initiated by Jay Akridge, provost and executive vice president for academic affairs and diversity, and Suresh Garimella, executive vice president for research and partnerships, the initiative has been formulated through two cross-campus working groups, forums and input from campus-wide discussions.
Office of the Provost announces request for proposals to build integrative data science education ecosystem