Nathaniel M. Byers, PhD

Position title: Friesen Laboratory 2010-2016

Research Title: Baculoviruses Manipulate the Host DNA Damage Response and Apoptosis to aid Virus Multiplication

Project Summary: Nathaniel Byers investigated the interactions between viruses and their host cells that determine cell fate and virus pathogenesis.  In particular, he studied how DNA viruses trigger apoptosis by engaging the host’s DNA damage response (DDR).  Because of their experimental advantages and the vigor with which they multiply, Nate used the large DNA baculoviruses as his model. These prolific insect viruses have provided important understanding of the pathways of virus-induced apoptosis that are relevant to human pathogenic viruses and human diseases, including cancer and neurodegenerative disorders. Within the Friesen laboratory, Nate studied the molecular mechanism by which the baculoviruses triggered the DDR, which initiated apoptosis but was also used to expedite viral DNA replication. To this end, the virus encoded powerful apoptotic suppressors and a replicative factor (LEF -7) that manipulated the host DDR. LEF-7 is a newly recognized F –box protein that blocks accumulation of phosphorylated histone H2AX, which is a critical regulator of the DDR. Nate hypothesized that by acting as a component of SCF ubiquitin ligase complex, LEF-7 targets a yet-to-be-identified DDR protein for degradation or modification. He has shown that LEF-7 is a pan-nuclear protein that overlaps with host chromatin and virus replication centers early in infection. He also identified candidate host proteins that interact with LEF-7 and therefore represent potential DDR targets.

Dr. Byers is continuing his training as a postdoctoral trainee at the Centers for Disease Control and Prevention.