2017 NIH SCAP-T: Single-cell approaches to infectious disease

(Stephen Fisher) #1

Thurs, June 29th, Breakout Session

Moderator: John Yin (University of Wisconsin–Madison)

Transmission of infectious diseases from ailing to healthy hosts occurs through a cough or sneeze, handshake, faucet handle, or mosquito’s bite. Typically, the process transfers a few bacterial cells or virus particles. Although a small number of cells or particles encounter a few susceptible host tissues or cells, the resulting infection initiates a battle — with potentially critical outcomes. The behavior of a few host cells infected by a small number of bacteria or virus particles can give rise to large ‘noise’ and significant variability in gene expression by the pathogen to amplify itself or by the host to set innate immune blockades, which then influence how further cycles of host cell or tissue infection amplify or inhibit the pathogen. The result can often be a diversity of symptoms and disease severities for patients, from mild to serious, or even deadly.

Questions for the breakout session to consider include:

  • To what extent do genetic, environmental, or other (stochastic) factors contribute to extremely heterogeneous distributions of virus production (yield) from single cells?
  • What are key challenges and opportunities for advancing innovative technologies to enable routine high-throughput single-cell measurements?
  • How can the intrinsic heterogeneity of single-cell readouts be exploited to extract new insights into virus-cell interactions?
  • How can systems biology approaches (mathematical modeling, computer simulations) add value to enable mechanistic interpretation of single-cell data?
  • What features of virus or cellular behaviors at the single-cell level most impact the severity of infection in natural hosts? (Note: Most infections in nature are initiated by small numbers of host cells initially becoming infected. From an evolutionary perspective, transmission can create genetic bottlenecks for the pathogen.)