Santa Fe Institute Collaboration Platform

COMPLEX TIME: Adaptation, Aging, & Arrow of Time

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Contact: Caitlin Lorraine McShea, Program Manager, cmcshea@santafe.edu

Aging and Adaptation in Infectious Diseases

From Complex Time

Category: Application Area

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

Location: Santa Fe Institute

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Organizers

  • Jean Carlson (UCSB)

  • Mercedes Pascual (Univ. Chicago)

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    Attendees
    Agenda/Schedule
    Click each agenda item's title for more information.
    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)

    How does our working group interface with overarching goals of the research program

    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[edit source]

    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[edit source]

    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[edit source]

    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[edit source]

    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).

    Post-meeting Summary by Organizer[edit source]

    Lorem ipsum dolor sit amet, consectetur adipiscing elit. Phasellus dui nunc, cursus eget facilisis in, pharetra vitae mauris. In hac habitasse platea dictumst. Vestibulum in aliquet ipsum. Phasellus nec mauris sit amet felis tempus accumsan eu tincidunt est. Donec rutrum egestas turpis, a vestibulum leo ultrices id. Ut iaculis finibus mauris sit amet pellentesque. In semper finibus commodo. Ut elementum, quam in efficitur molestie, dui lectus blandit sem, sit amet consequat dui erat mollis ligula. Duis pretium tempor neque, eu rutrum ipsum tempus non. Nulla id tristique nibh.

    Additional Post-meeting Summary by Organizer
    What was the big question or idea the meeting was designed to explore?
    EXPLORE
    What disciplines/fields were represented at the meeting?
    Nullam mollis, ante in lobortis eleifend, dui turpis sodales orci, sed scelerisque quam lorem eget lectus. Aliquam et ornare sem. Pellentesque a luctus quam, quis blandit orci.
    What one or two new research direction(s) did the meeting suggest?
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    What was the most interesting thing said during the meeting, and who said it?
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    What idea from the meeting is likely to be most impactful for science?
    idea from the meeting is likely to be most impactful for science
    What idea from the meeting is potentially translatable into an application?
    idea from the meeting is potentially translatable into an application
    What new method/technology/algorithm/etc. resulted (or may result) from this meeting?
    new method/technology/algorithm/etc. resulted (or may result) from this meeting

    A narrative summary of the meeting

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    Vestibulum porta felis pretium, luctus justo id, elementum ipsum. Curabitur eleifend laoreet convallis. Pellentesque nec luctus turpis, sit amet faucibus arcu. Integer vulputate pharetra dolor, ut eleifend neque finibus ut. Duis ex urna, efficitur rutrum rutrum id, accumsan sit amet ligula. Nullam mollis, ante in lobortis eleifend, dui turpis sodales orci, sed scelerisque quam lorem eget lectus. Aliquam et ornare sem. Pellentesque a luctus quam, quis blandit orci. Sed porta pulvinar dictum. Donec facilisis pretium gravida. Sed ultrices turpis ac velit semper imperdiet. Donec dictum, eros ut elementum aliquet, tortor metus pretium erat, eget posuere lorem nunc quis sapien. Sed nec elit tempor, rutrum quam vel, ultrices purus. Etiam posuere orci lorem, ut mattis felis condimentum sit amet. Donec quis faucibus dolor, porta porta nulla. In consectetur felis eu mi interdum, at consequat dui semper.

    Nulla at neque metus. Aliquam vulputate, nibh id placerat vehicula, sapien felis feugiat est, a malesuada libero ligula id felis. Vivamus vel volutpat elit, ac ultrices sapien. Nulla eu arcu eget libero faucibus molestie. Ut a lobortis sapien, eget tincidunt enim. Nullam eget lectus nisi. Donec id eros pellentesque, rutrum massa id, pharetra nulla. Duis laoreet scelerisque justo. Phasellus egestas erat quam.

    Nam non imperdiet leo. Cras bibendum leo massa, at dapibus massa tincidunt at. Donec accumsan ex vel mauris ultricies dignissim. Nunc sodales leo dolor, in sollicitudin augue faucibus non. Proin posuere risus vitae turpis facilisis facilisis. Sed sagittis quam ante, non condimentum mauris ultricies eu. Fusce fermentum lorem ac dolor aliquet egestas. Fusce blandit varius neque id posuere. Curabitur commodo euismod metus eu vehicula. Class aptent taciti sociosqu ad litora torquent per conubia nostra, per inceptos himenaeos.

    Integer gravida, libero vel auctor maximus, quam justo ultricies eros, ut fermentum turpis velit et nibh. Sed aliquet enim ipsum, sed tempus metus blandit in. Nunc varius ante id porta faucibus. Nulla mattis, orci sit amet vulputate efficitur, enim dui commodo quam, eu tempus dui eros at lectus. Vivamus tempus odio mattis mollis dictum. Aenean fringilla, arcu eu porta tincidunt, mauris augue hendrerit neque, vitae ultricies neque risus et dui. Aliquam non elit quam. Curabitur tempor, neque eget venenatis tincidunt, magna massa vestibulum ipsum, sit amet tincidunt massa leo sed lorem. Curabitur mi turpis, fringilla quis felis nec, vulputate mollis purus. Cras blandit metus eu odio rhoncus posuere.

    Outcomes that might emerge from the meeting

    Phasellus dui nunc, cursus eget facilisis in, pharetra vitae mauris. In hac habitasse platea dictumst. Vestibulum in aliquet ipsum. Phasellus nec mauris sit amet felis tempus accumsan eu tincidunt est. Donec rutrum egestas turpis, a vestibulum leo ultrices id. Ut iaculis finibus mauris sit amet pellentesque. In semper finibus commodo. Ut elementum, quam in efficitur molestie, dui lectus blandit sem, sit amet consequat dui erat mollis ligula. Duis pretium tempor neque, eu rutrum ipsum tempus non. Nulla id tristique nibh.

    Communication produced related to the meeting

    Vestibulum porta felis pretium, luctus justo id, elementum ipsum. Curabitur eleifend laoreet convallis. Pellentesque nec luctus turpis, sit amet faucibus arcu. Integer vulputate pharetra dolor, ut eleifend neque finibus ut. Duis ex urna, efficitur rutrum rutrum id, accumsan sit amet ligula. Nullam mollis, ante in lobortis eleifend, dui turpis sodales orci, sed scelerisque quam lorem eget lectus. Aliquam et ornare sem. Pellentesque a luctus quam, quis blandit orci. Sed porta pulvinar dictum. Donec facilisis pretium gravida. Sed ultrices turpis ac velit semper imperdiet. Donec dictum, eros ut elementum aliquet, tortor metus pretium erat, eget posuere lorem nunc quis sapien. Sed nec elit tempor, rutrum quam vel, ultrices purus. Etiam posuere orci lorem, ut mattis felis condimentum sit amet. Donec quis faucibus dolor, porta porta nulla. In consectetur felis eu mi interdum, at consequat dui semper.

    Post-meeting Reflection by Presenter

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

    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[edit source]

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

    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 7 8
    Evidence of strain structure in Plasmodium falciparum var gene repertoires in children from Gabon, West Africa 0 8

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

    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 7 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[edit source]

    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 105 25
    Reference Materials by Non-presenting Attendees


    General Meeting Reference Material[edit source]