GROUP LEADER: Nicholas Stroustrup

GRADUATE STUDENTS: Olivier Martin, Monika Anna Matusiak Bruckner, Natasha Oswal (new in 2018)

POSTDOCTORAL RESEARCHER: Rute Fernandes (Marie Curie Fellow)

BIST MASTER’S STUDENT: Emanuelle Fara

SUMMARY

The goal of our research is to understand how molecular and cellular-level produce age-related declines in health and ultimately determine the timing of death.  In multicellular animals, aging involves diverse set of physiologic declines observed across multiple levels of biological organization, from molecules and cells to tissues and organ systems. It remains a fundamental challenge in biology to build predictive models of how these levels interact to determine organism-level physiologic properties.  I study this in the context of the aging of C. elegans, a small multicellular animal in which single base pair substitutions can extend lifespan three-fold and a variety of environmental, small-molecule, and dietary interventions have been shown to influence aging.  The plasticity of lifespan (a quantitative systemic phenotype) and the diversity of molecular-level interventions allows us to run physics-inspired experiments relating whole-animal physiology to the action of individual genes.  As enthusiasm grows to develop clinical interventions in human aging, it will become increasingly important to develop frameworks that allow us to understand the systemic action of new classes of pharma- and neutral-ceuticals.  My group pursues these goals through a combination of experimental work in C. elegans, theoretic projects involving complex networks, and technological development involving our high-throughput imaging technology.

Measuring the effect of interventions on the distribution of lifespan. The survival curves measured for a) daf-16 mutants and b) wildtype animals exposed to varying concentrations of tert-butyl hydroperoxide. (Stroustrup et al. 2016)

Fig. 1

Measuring the effect of interventions on the distribution of lifespan. The survival curves measured for a) daf-16 mutants and b) wildtype animals exposed to varying concentrations of tert-butyl hydroperoxide. (Stroustrup et al. 2016)

Relating interventions in aging to individual physiologic variation. a) Changes in the distribution of lifespan of individuals can be related to b) early-life physiologic changes (Stroustrup et. Al 2016; Zhang WB et al. 2016)

Fig.2

Relating interventions in aging to individual physiologic variation. a) Changes in the distribution of lifespan of individuals can be related to b) early-life physiologic changes (Stroustrup et. Al 2016; Zhang WB et al. 2016)

RESEARCH PROJECTS

  • Identifying aging processes through their action on lifespan distributions
    My group builds on the techniques I developed as a post-doc, characterizing physiologic aging processes through careful measurement of their effect on lifespan distributions.
  • Measuring and modelling stochastic aging processes
    My group is working to relate deterministic and stochastic aspects of aging processes. This involves the development of theoretic models (drawn from statistical physics and complex networks analysis) and experimental work combing C. elegans genetics and transcriptomics.
  • High-throughput Imaging
    Supporting our lifespan distribution project, my group continues to develop the high-throughput imaging technology I developed as a graduate student, the Stroustrup et al. C. elegans lifespan machine.

SELECTED PUBLICATIONS

Lin XX, Sen I, Janssens GE, Zhou X, Fonslow BR, Edgar D, Stroustrup N, Swoboda P, Yates JR 3rd, Ruvkun G, Riedel CG.
“DAF-16/FOXO and HLH-30/TFEB function as combinatorial transcription factors to promote stress resistance and longevity.”
Nat Commun, 9(1):4400, 2018. doi: 10.1038/s41467-018-06624-0.

Stroustrup N.
“Measuring and modeling interventions in aging.”
Curr Opin Cell Biol, 55:129-138, 2018. doi: 10.1016/j.ceb.2018.07.004. Epub 2018 Aug 10. Review.