Santa Fe Institute Collaboration Platform

COMPLEX TIME: Adaptation, Aging, & Arrow of Time

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Contact: Amy P. Chen, Program Manager, amypchen@santafe.edu

Aging and Adaptation in Infectious Diseases

From Complex Time

Category: Application Area Application Area: Infectious Diseases

Date/Time: July 26, 2018 - July 28, 2018

Location: Santa Fe Institute (Noyce Conference Room)

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Organizers

  • Mercedes Pascual (Univ. Chicago)

  • Jean Carlson (UCSB)

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    Attendees

    Agenda/Schedule
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    Thursday, July 26, 2018
    8:30 am - 9:00 am Day 1 Continental Breakfast (outside SFI Noyce Conference Room)
    9:00 am - 9:15 am Welcome - Amy P Chen (SFI), David Krakauer (SFI), Susan Fitzpatrick (JSMF) Download Presentation
    9:15 am - 9:30 am Introductions and Workshop Overview - Jean Carlson (UCSB), Mercedes Pascual (Univ. Chicago)
    9:30 am - 11:30 am Session I: Immune System Dynamics and Age - Mercedes Pascual (Univ. Chicago)
    1. Host heterogeneity in susceptibility to infectious and inflammatory diseases across the lifespan - Andrea L. Graham (Princeton) Download Presentation
    2. Infection trajectories through time and age - David Schneider (Stanford)
    3. Theoretical Immunology: Aging - Alan Perelson (LANL/SFI) Download Presentation
    11:30 am - 1:00 pm Day 1 Lunch (outside SFI Noyce Conference Room)
    1:00 pm - 3:00 pm Session IIA: Viral Evolution, Dynamics, and Therapies - Jean Carlson (UCSB)
    1. How to hit HIV where it hurts, with a splash of how the immune system ages - Arup K. Charaborty (MIT)
    2. Evolving antibody repertoire to vaccine and virus: evolutionary arms race and ecological feedback - Shenshen Wang (UCLA) Download Presentation
    3. Aging and immunity to influenza - Sarah Cobey (Univ. Chicago)
    3:00 pm - 3:30 pm Day 1 PM Break
    3:30 pm - 5:00 pm Session IIB: Viral Evolution, Dynamics, and Therapies - Sarah Cobey (Univ. Chicago)
    1. Do viruses age? Temporal trends in endemically circulating viruses - Katia Koelle (Emory Univ.) Download Presentation
    2. Evolution of life-history trade-offs in viruses andin virotherapy - Paul Turner (Yale) Download Presentation
    6:30 pm Day 1 Group Dinner at La Choza
    Friday, July 27, 2018
    8:30 am - 9:00 am Day 2 Continental Breakfast (outside SFI Noyce Conference Room)
    9:00 am - 9:30 am SFI/JSMF Aging, Adaptation, and the Arrow of Time Research Theme; Overview - Jean Carlson (UCSB), Mercedes Pascual (Univ. Chicago), David Krakauer (SFI), Susan Fitzpatrick (JSMF)

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    9:30 am - 11:30 am Session III: Host Pathogen (co)Adaptation, Diversification, and Age - Andrea L. Graham (Princeton)
    1. Robustness and fragility in adaptive immunity: Immunosenescence and host-pathogen coevolution - Jean Carlson (UCSB) Download Presentation
    2. Time, adaptation and host specialization in host-parasite interactions - Noah K. Whiteman (UC Berkeley) Download Presentation
    3. Parasite (antigenic) diversity and ‘old’ and resilient transmission systems - Mercedes Pascual (Univ. Chicago) Download Presentation
    11:30 am - 1:00 pm Day 2 Lunch (outside SFI Noyce Conference Room)
    1:00 pm - 3:00 pm Session IV: Complex Rhythms, environment, and aging in epidemiology - David Schneider (Stanford)
    1. Social gradients in nonhuman primates: linking social status to immune gene regulation - Jenny Tung (Duke Univ.) Download Presentation
    2. Infectious diseases across scales, circadian rhythms: Anticipating Complex Time - Micaela Martinez (Columbia Univ.) Download Presentation
    3. Insights into aging and pathogens from allometrically scaled models for host-parasite systems - Andrew P. Dobson (Princeton) Download Presentation
    3:00 pm - 3:30 pm Day 2 PM Break
    3:30 pm - 5:00 pm Discussion, development of themes, and organization of breakout groups
    6:30 pm Day 2 Group Dinner at Restaurant Martin
    Saturday, July 28, 2018
    8:30 am - 9:00 am Day 3 Continental Breakfast (outside SFI Noyce Conference Room)
    9:00 am - 11:00 am Breakout Group Discussions
    11:00 am - 12:00 pm Group Presentations and Plans for Next Steps
    12:00 pm - 1:00 pm Day 3 Lunch (outside SFI Noyce Conference Room); Adjourn

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    Meeting Synopsis

    This working group explores the role of aging and adaptation in infectious diseases operating over multiple organizational and temporal scales. General areas include immune system dynamics and age, host-pathogen co-adaptation in chronic vs. acute infections, pathogen antigenic diversity and endemism, effects of age on infectious diseases in human and nonhuman hosts. Overarching themes include memory, (co)adaptation, diversity, feedback, robustness and fragility. We are interested in aging and biological time as reflecting a loss of robustness in the face of infection at the level of individuals but also populations. We are also interested in aging of the pathogen in relation to its ability to persist and withstand intervention efforts. This meeting brings together a select group of scientists from a range of backgrounds to define novel questions, facilitate potential collaborations, and catalyze new and transformative research in this area. Development of methods that combine big data, experiments, theory, and computation with predictive and therapeutic applications across disciplines is of particular interest.

    Additional Meeting Information

    Overview and rationale

    Time and age in standard dynamical systems for infectious diseases are treated as simple clocks that run at a constant rate. Thus, standard epidemiological models that incorporate host age consider structured populations and rely on partial differential equations in which the derivative of age relative to time is simply a constant. By contrast, ‘complex’ time in infectious disease dynamics is intimately related to the different trajectories that either individuals or populations can follow and which ultimately determine the outcome of infection, its susceptibility to intervention, and the likelihood of critical failure. Pieces of what determines these trajectories have been investigated, in relation to the immune system, pathogens’ evolution and their escape from the host’s acquired memory, as well as the coadaptation of both. A synthesis of these efforts and a general theory that places aging at its center is still missing.

    We have been purposefully vague so far on whose age we are considering. Age of the host is only one possibility. There is also the age of first infection and that of pathogen lineages and their persistence through time. Another age is that of infection in a population, from the short duration of epidemics to the long-lasting persistence of endemic diseases. All these quantities are inter-related, in some cases in ways we already understand. What is missing is a deeper understanding and synthesis of the variable outcomes and temporal trajectories of disease at different levels of organization. Some individuals may experience fatal failure to recover from disease, others may tolerate infection and exhibit a robust path to recovery. In endemic locations, under high transmission, a large reservoir of asymptomatic infection can lead to persistence of the pathogen and its resilience to intervention. The same disease under low transmission will be epidemic and possibly easier to eliminate.

    At the center of these outcomes are both the acquisition of information by the immune system and the antigenic escape of pathogens. Thus, information, diversity and adaptation are central themes influencing the outcome of disease and intervention in relation to age. They are also common themes with other efforts of the JSMF initiative at SFI.

    Meeting organization

    The first two days of the working group each begin with a general discussion of broad themes and goals associated with the working group and the JSMF/SFI Aging and the Arrow of Time initiative followed by participant introductions by way of research presentations. The presentations are broken into complementary topical sessions which include (i) immune system dynamics and age, (ii) viral evolution and therapies (sessions A and B) (iii) host-pathogen (co)adaptation, diversification, and age, and (iv) complex time, environment, and aging in epidemiology.

    Each topical session will consist of 30-minute talks at a high enough level that everyone can follow. A 30-minute discussion session is scheduled at the end of each topical session, designed to explore themes and challenges arising in the session.

    The second day concludes with a discussion of emerging themes and opportunities for transformative research. The working group will identify novel questions for further development by 3-4 breakout groups on day three, designed to identify opportunities for future research and collaboration. The breakout groups will report back with summary presentations at the conclusion of the final day of the meeting.

    Abstracts by Presenters

    Micaela Martinez (Columbia Univ.) - Session IV: Complex Rhythms, environment, and aging in epidemiology

    The meeting is composed of expert disease dynamicsmodelers and disease ecologists; thus, my presentation will be focused on chronobiology. Specifically, I will review new data regarding circadian and circannual rhythms in humans and mouse models.

    Andrew P. Dobson (Princeton) - Session IV: Complex Rhythms, environment, and aging in epidemiology

    Assemble a talk that describes non-human examples of how host exposure and response to pathogens and disease changes with age.

    Describe ways of quantifying age-dependent changes in exposure.

    Discuss possible dynamic consequences in variation in duration of incubation and infectivity with age.

    Describe models for parasitic nematodes of different sizes living as a community of worms in hosts of different sizes.

    Illustrate recent work with Ian Hatton on body size scaling of vital rates from Algae to Elephants - use this to suggest we could use this scaling for models of immune system in mammals (from bats and mice to elephants and whales).

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    Post-meeting Reflection by Presenter

    Andrew P. Dobson (Princeton) - Session IV: Complex Rhythms, environment, and aging in epidemiology Link to the source page

    Really interesting set of talks that blended into a good set of discussions on projects the group could work on. There will be a big emphasis on human immunity and how it first gains 'experience' and then breaks down with age.

    I'm likely to focus my attention on developing body sized scaled models for immune system. These could be both fairly simple models for immunity mainly capturing differences between Type I and Type II immunity, but then expanding this to take Jean Carlson's model for human immunity and rescale elements of this with host body size and BMR.

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    Post-meeting Reflection by Non-presenting Attendees

    Reference Materials by Presenting Attendees

    Mercedes Pascual (Univ. Chicago) - Session I: Immune System Dynamics and Age, Session III: Host Pathogen (co)Adaptation, Diversification, and Age

    Title Author name Source name Year Citation count From Scopus. Refreshed every 5 days. Page views Related file
    Networks of genetic similarity reveal non-neutral processes shape strain structure in Plasmodium falciparum Qixin He, Shai Pilosof, Kathryn E. Tiedje, Shazia Ruybal-Pesántez, Yael Artzy-Randrup, Edward B. Baskerville, Karen P. Day, Mercedes Pascual Nature Communications 2018 3 8
    Evidence of strain structure in Plasmodium falciparum var gene repertoires in children from Gabon, West Africa 0 8

    Jenny Tung (Duke Univ.) - Session IV: Complex Rhythms, environment, and aging in epidemiology

    Title Author name Source name Year Citation count From Scopus. Refreshed every 5 days. Page views Related file
    Social status alters immune regulation and response to infection in macaques Noah Snyder-Mackler, Joaquín Sanz, Jordan N. Kohn, Jessica F. Brinkworth, Shauna Morrow, Amanda O. Shaver, Jean Christophe Grenier, Roger Pique-Regi, Zachary P. Johnson, Mark E. Wilson, Luis B. Barreiro, Jenny Tung Science 2016 58 23
    Reference Materials by Non-presenting Attendees


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