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MISSION

The Ivanovic lab investigates the molecular mechanisms of viral cell entry and progeny particle assembly. We combine molecular virology, in vitro reconstitution, biophysics, and quantitative cell biology to answer difficult-to-tackle mechanistic questions in virology, and build upon those discoveries to ultimately enable prediction and prevention of undesirable viral adaptation (e.g. drug resistance, immune escape, or pandemic adaptation). Our work spans diverse viral pathogens and/or their model systems, such as influenza virus, Ebola virus, coronavirus, reovirus, respiratory syncytial virus, and Measles virus.

RESEARCH INTERESTS

Viral outbreaks and pandemics arise when animal viruses adapt so that they can recognize and use human cells as their host. Viral persistence in human circulation is subsequently driven by rapid acquisition of mutations in viral proteins that allow evasion of the adaptive human immune response. Recent research in the Ivanovic lab has shown that viral ability to recognize and invade host cells in the presence of the immune-system antibodies is determined by the viral particle structure. For example, the same antibodies binding to the same target viral protein may or may not neutralize viral infection depending on the overall structural organization of the virus particle displaying these targets. We are further working to define how the structural organization of virus particles might enable entry into cells not displaying fitting receptors. Viral ability to establish new infections under suboptimal conditions is probed as a possible mechanism of adaptation to new hosts with a potential to lead to new pandemics. Complementing our research on virus cell entry is our effort to define the mechanisms of virus particle assembly and regulation of the assembly outcomes (i.e. structural features of virus particles such as shape, size, or viral protein incorporation). We have developed novel quantitative and high-throughput approaches for studying virus particle assembly, and detailed functional characterizations are under way.

ONGOING PROJECTS

• Viral cell-entry and assembly mechanisms
• Virus particle shape regulation in pleomorphic viruses
• Structure/function relationship for uniformly shaped, icosahedral virus particles
• Viral adaptation – crosstalk between phenotypic and genetic diversity
• Novel antivirals

EXPERIMENTAL TOOLKIT

Our research integrates molecular virology, cell biology, single-molecule biophysics, and computational modeling. As a result, trainees in the Ivanovic lab learn not only how to think deeply as virologists, but also acquire an unusual combination of interdisciplinary skills that together permit them to seek answers to sophisticated questions.

RECENT PUBLICATIONS

• Li Z, Li T, Liu M, Ivanovic T. Hemagglutinin stability determines influenza A virus susceptibility to a broad-spectrum fusion inhibitor Arbidol. ACS Infect. Dis. https://doi.org/10.1021/acsinfecdis.2c00178 [Editor’s Choice]
• Li T, Li Z, Deans EE, Mittler E, Liu M, Chandran K, Ivanovic T. The shape of pleomorphic virions determines resistance to cell-entry pressure. Nat. Microbiol. 6(5):617-629. Epub 2021 [PDF]

JOB OPENINGS

Postdoctoral Fellow positions 
FEATURED: Exciting new opportunity for a postdoc in viral biology and biophysics at the NIH! The Ivanovic lab is in search of a talented and motivated postdoctoral researcher to join us in the Laboratory of Viral Diseases in NIAID at the NIH in early 2023.

CURRENT LAB MEMBERS

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