The Mahoney brothers all received their degrees in Chemistry from the University of Massachusetts Amherst. They went on to become leaders in their own industries and have served as high-level alumni advisers to the campus. The Mahoney brothers encourage the university to think differently about the way it serves its students and promotes the UMass Amherst education. Their commitment to student success is seen in their extraordinary efforts to personally mentor students and train other alumni to do the same, while their family legacy of giving and involvement is seen far and wide throughout the campus. The Mahoney Life Sciences Prize, like all that this family does for its alma mater, seeks to inspire and recognize greatness.
Past Mahoney Prize Recipients
Dr. Derek R. Lovley
Distinguished Professor, Department of Microbiology 2020 Recipient
Ueki, T., Walker, D. J. F., Tremblay, P.-L., Nevin, K. P., Ward, J. E., Woodard, T. L., Nonnenmann, S. S., & Lovley, D. R. (2019). Decorating the Outer Surface of Microbially Produced Protein Nanowires with Peptides. ACS Synthetic Biology, 8(8), 1809–1817. https://doi.org/10.1021/acssynbio.9b00131
The potential applications of electrically conductive protein nanowires (e-PNs) harvested from Geobacter sulf urreducens might be greatly expanded if the outer surface of the wires could be modified to confer novel sensing capabilities or to enhance binding to other materials. We developed a simple strategy for functionalizing e-PNs with surface-exposed peptides. The G. sulf urreducens gene for the monomer that assembles into e-PNs was modified to add peptide tags at the carboxyl terminus of the monomer. Strains of G. sulf urreducens were constructed that fabricated synthetic e-PNs with a six-histidine “His-tag” or both the His-tag and a nine-peptide “HA-tag” exposed on the outer surface. Addition of the peptide tags did not diminish e-PN conductivity. The abundance of HA-tag in e-PNs was controlled by placing expression of the gene for the synthetic monomer with the HA-tag under transcriptional regulation. These studies suggest broad possibilities for tailoring e-PN properties for diverse applications.
Dutta, K., Hu, D., Zhao, B., Ribbe, A. E., Zhuang, J., & Thayumanavan, S. (2017). Templated Self-Assembly of a Covalent Polymer Network for Intracellular Protein Delivery and Traceless Release. Journal of the American Chemical Society, 139(16), 5676–5679. https://doi.org/10.1021/jacs.7b01214
Protein-based drugs have great potential for improving our ability to treat disease. In comparison to current drugs that are based on small molecules, drugs composed of proteins are more effective for addressing specific genetic deficiencies without undesirable side effects. However, there are major challenges in delivering proteins into and within a cell. These challenges are related to keeping the protein stable, avoiding unwanted immune system response, and translocating the protein across the cellular membrane.
This study presents a novel and practical strategy which simultaneously overcomes all of these challenges. In this strategy, the polymers self-assemble to form a sheath around the protein, analogous to "shrink-wrapping" the protein. The polymer sheath encapsulates proteins, preserves their structure and function during delivery, and releases them when the assembly enters the cell cytosol. The polymers do not provoke an unwanted immune system response, and do not leaving any residue behind. This strategy is applicable to a broad range of proteins, and the sheath can be designed to release its cargo under various conditions. In addition to the applications for protein therapeutics and devices, the technology can be used to design reagents for basic biochemical research. Dr. Thayumanavan is currently working with industry partners toward both applications, in part through his start-up company, Cyta Therapeutics.
Associate Professor, Department of Chemistry 2018 Recipient
Dagbay, K. B., & Hardy, J. A. (2017). Multiple proteolytic events in caspase-6 self-activation impact conformations of discrete structural regions. Proceedings of the National Academy of Sciences, 114(38), E7977–E7986. https://doi.org/10.1073/pnas.1704640114
The challenges wrought by Alzheimer's disease are increasing with the graying of society in the developed world. In the United States, Alzheimer's disease promises to be the single largest medical expense ($1.1 trillion annually) by 2050. Today, no suitable treatments for Alzheimer's disease exist. Associate Professor in Chemistry Jeanne Hardy has been working for more than a decade to understand an important protein involved in Alzheimer's disease, called caspase-6. Recently, Dr. Hardy made important discoveries that may significantly advance our ability to treat this increasingly relevant disease.
People with Alzheimer's disease have tangles associated with the neurons of their brains. There is evidence that the caspase-6 protein is responsible for creating those tangles. Inhibiting caspase-6 could be one of the most promising approaches for treating Alzheimer's disease. In order to do this with a positive outcome, it is important not to inhibit any of the other 11 caspases. This is a major challenge, because all of the caspase proteins perform very similar reactions.
Dr. Hardy has risen to this challenge. In 2011, the Hardy lab found that one part of caspase-6 can fold into a helix, which no other caspase can do. However, caspase-6 does not maintain a helix shape all of the time, but constantly fluctuates between a helix and a three-strand shape. Last year, the Hardy lab used a state-of-the-art method to take snapshots of what parts of caspase-6 change shape and fluctuate over time. Insights from this study have allowed the Hardy Lab to develop new chemicals, targeting caspase-6 without affecting other caspases. This development represents a pivotal step forward toward treating Alzheimer's disease with caspase-6 inhibitors.