Development of Improved Insecticides for Malaria Vector Control

SPG scientists solved structures of the G119S mutant acetylcholinesterase that confers insecticide-resistance, emerging in the malaria mosquito.  This work will aid in the design of new resistance-breaking insecticides to help reduce malaria transmission in developing countries.  Cheung et al.  Structure.  26(1): 130-136 (2018).

Antibody Epitope Mapping
SPG Scientists solved the structures of the ricin toxin in complex with neutralizing antibodies to gain critical information for the design of ricin vaccines. Rudolph et al. J Mol Biol. 426(17): 3057-68 (2014)

Structural Consequences of Cancer Mutations
SPG Scientists solved the structure of several mutant proteins associated with two different forms of cancer and identified different mechanisms of disease for each. In adrenal cancer, a point mutation abolishes binding of a regulatory protein. In liver cancer, a fusion event increases PKA expression levels. Cheung et al. PNAS 112, 1374 (2015)

Structure-Guided Antibody Design
SPG Scientists identified the mechanisms by which therapeutic antibodies neutralize Staphylococcal Enterotoxin B (SEB) and developed strategies to extend their neutralizing properties to other, related toxins. Dutta et al. J Biol Chem. 290(11): 6715-30 (2015)

High Throughput Structural Biology
SPG scientists solved the structure of 48 proteins from the highly infectious bacterium Coxiella burnetii. They identified differences with a key human DHFR to develop bacterial-specific small molecule inhibitors. Franklin et al. Proteins PMID: 26033498 (2015)

Development of a platform for rational drug design
SPG scientists developed a novel platform to search for small molecules to protect human acetylcholinesterase from nerve agents. Cheung et al. J Mol Neurosci. 53(3):506-10 (2014)

Rapid Antibacterial Drug Discovery
SPG scientists determined the crystal structures of enzymes critical for the growth and survival of Francisella tularensis, a pathogen that causes tularemia, a potentially fatal disease. This data led to the identification of several novel antimicrobial compounds. Chaudhury et al. PLoS One. 8(5):e63369 (2013).