Work from the laboratory of John MacMicking in the Yale Systems Biology Institute was recently named one of 10 innovative discoveries for 2021, according to the Smithsonian magazine.
MacMicking’s team reported in Science that a human protein called apolipoprotein L3 (APOL3) acts like a detergent to kill bacterial pathogens inside human cells. This finding was unexpected since detergent activity could also harm host cell membranes. Cholesterol – a major constituent of human but not bacterial membranes – was shown to interfere with APOL3 binding, thereby protecting the host and enabling APOL3 to discriminate friend from foe.
MacMicking and his colleagues hope to extend these discoveries to other important human pathogens including viruses, parasites, and fungi. Reproducing the natural behavior of APOL3 using small molecules could also help tackle antibiotic resistance and offer new treatment options for infections where drugs are currently unavailable. For these reasons the Smithsonian Institute named this work a potential source of invention.
Dr. MacMicking is a Howard Hughes Medical Institute (HHMI) Investigator who was recently renewed for another 7-year term. Future work on APOL3 will therefore continue to be supported by HHMI, along with YSBI and the Yale School of Medicine, where he is an associate professor in the Departments of Microbial Pathogenesis and Immunobiology.