Bonnie Bassler of Princeton University and the Howard Hughes Medical Institute has revolutionized the way that we think about microbiology. She elucidated the chemical language that bacteria use to communicate through a process called quorum sensing that allows bacteria to count their numbers, determine when they’ve reached a critical mass, and then change their behavior in unison to result in virulence or even bioluminescence. Called everything from a [MacArthur] genius to the bacteria whisperer, Bassler also excels at the art of scientific communication, has dabbled in theater, and many mornings a week leads an aerobics class in Princeton.
Broadly neutralizing antibodies (BnAbs) represent a promising strategy for targeting rapidly mutating viruses, such as HIV-1. BnAbs recognize conserved epitopes and display unique characteristics that suggest that their development may be limited by immune tolerance. In this episode, Baton Haynes discusses the identification and characterization of a BnAb in an HIV-1-infected individual that developed the autoimmune disease systemic lupus erythematosus. The BnAb targeted both the HIV-1 envelope and human antigens, including dsDNA, supporting the hypothesis that lax immune control allows for maturation and production of BnAbs.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly forms of cancer, primarily due to the resistance of PDAC tumors to current therapeutic strategies. Several lines of evidence suggest that ineffective delivery of chemotherapy agents to tumor cells in the pancreas contributes to PDAC-associated treatment resistance. In this episode, Eugene Koay and Jason Fleming discuss the results of their clinical study that links pancreatic transport properties collected from PDAC patient CT scans with survival and response to the chemotherapy agent gemcitabine.
Familial Alzheimer's disease (FAD) is an early on-set, hereditary form of neurological disease with variable pathophysiology that is often associated with loss of cerebellar function and amyloid plaque formation. Diego Sepulveda-Falla and colleagues investigated how a particular PS1 mutation (PS1-E280A), present in large Columbian kindred of FAD patients, promotes disease. Postmortem evaluation of cerebellar tissue from patients revealed that PS1-E280A is associated with Purkinje cell loss, an abundance of abnormal mitochondria and loss of calcium transport proteins. Furthermore, cell culture and murine models of PS1-E280A FAD revealed that PS1alterations disrupt calcium homeostasis and mitochondrial transport within cerebellar neurons, resulting in increased amyloid plaque formation and cerebellar dysfunction.
After a 15-year focus on the biology of the hepatitis B virus (HBV) family, the modern-day microbe hunter Don Ganem turned his attention to KSHV, the herpes virus that is the cause of the AIDS-related neoplasm Kaposi sarcoma (KS). His lab at UCSF was the first to cultivate and develop tests for KSHV. In 2010, after nearly 30 years in academia, Ganem left for industry and is currently the Vice President and Global Head for Infectious Disease for the Novartis Institutes for Biomedical Research. View the full interview for many more stories about flunking algebra to hold hands with a girl, what Martians with golf clubs can teach you about drawing conclusions, and taking a turn as Dr. Dolittle.