Nav: Home

Wyss Institute to lead project to uncover underlying causes of tolerance to infection

May 31, 2016

(BOSTON) - The Wyss Institute for Biologically Inspired Engineering at Harvard University will lead a $9.9M multi-institutional, DARPA-funded effort including Harvard Medical School, the Mayo Clinic, Temple University, Tufts University, and Boston Children's Hospital in order to investigate why some host organisms are tolerant to pathogenic infection, and to uncover which biological mechanisms are responsible for their resilience.

The initiative, called Technologies for Host Resilience (THoR), will search for and identify examples of tolerance across several species through experiments with clinically-relevant pathogens, and will then develop a custom bioinformatics platform to reverse engineer and pinpoint multiple therapeutic targets that could one day be potentially used to induce tolerance in humans. Selected by DARPA to lead the initiative, the Wyss Institute has expertise in modeling systemic infection and sepsis in pigs (which in 2015 led to the development of a sepsis therapeutic device), an extremely large inventory of clinically-isolated pathogens numbering more than 200 in total, and unique organs-on-chips technology that enables in vitro analysis of human organ-level responses.

Led by Principal Investigator (PI) and Wyss Founding Director Donald Ingber, M.D., Ph.D., and Co-PI and Wyss Senior Staff Scientist Michael Super, Ph.D., the THoR team aims to uncover new molecular information about infection tolerance that will enable development of novel therapeutics.

"There's been recent recognition of the desperate problem of emerging infections and the rise of antibiotic resistance," said Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Children's Hospital, as well as Professor of Bioengineering at Harvard's John A. Paulson School of Engineering and Applied Sciences.

"Yet, at the same time," Ingber continued, "there is always a subpopulation of individuals who become infected but never display significant symptoms. DARPA has provided us with support to uncover how this works, with the visionary goal of developing an entirely new class of resilience-inducing therapeutics that can make everyone tolerant of infection, regardless of whether it's multidrug resistant bacteria, influenza, or Ebola."

Often it's not the infections themselves, but the inflammatory cascade of symptoms they trigger that leads to life-threatening complications associated with infections such as sepsis, organ injury, and even death. The team envisions that THoR could lead to new therapeutics that could one day protect patients from developing symptoms stemming from many different kinds of infections, while also allowing them to more quickly clear pathogens from their bodies.

"It's such a new approach to fighting pathogen infection - something that's never been done before - and it's incredibly exciting to be leveraging our expertise in modeling sepsis infection to make new discoveries about how some individuals or species fare better than others in the face of infection, and then apply this knowledge to develop novel therapies," said Super.

The THoR team will search across multiple species, including human, mouse, pig and frog, for tolerance-inducing biological mechanisms. To do so they will utilize organs-on-chips technology to compare how the microbiomes in human versus mouse guts influence tolerance to infection, and collect data using a pig infection model to identify and study tolerant individuals. Additionally, the team will develop the first-ever high-throughput screening method in frog embryos to screen for tolerance-inducing mechanisms. Frogs share common regulatory and immune systems with humans and other higher order organisms - because of this it's possible to screen through their embryos for a broad range of pathogens and thousands of potential therapeutic compounds much faster than using other experimental models.

A predictive and unified analysis platform based on integrated bioinformatics algorithms and modeling approaches will be developed to crunch through the voluminous experimental data generated by the team. These efforts will be led by co-investigator and Wyss Core Faculty member James Collins, Ph.D., who is also the Termeer Professor of Medical Engineering & Science and Professor of Biological Engineering at the Massachusetts Institute of Technology's Department of Biological Engineering.

"We intend to collect different kinds of high-throughput biomolecular data to identify the genetic and metabolic factors mediating tolerance in multiple higher organisms," said Collins. "From these comparative analyses, we ultimately want to understand how tolerance arises in humans. Our integrated systems approach is centered around the notion that biological networks underlie the tolerant responses of higher organisms to infections."

In addition to Ingber, Super, and Collins, other collaborators playing key roles in THoR will include: Dennis Kasper, M.D., the William Ellery Channing Professor of Medicine at Brigham and Women's Hospital and Professor of Microbiology and Immunobiology at HMS, who will assist in characterizing tolerance in human and mouse gut-on-a-chip devices; Hu Li, Ph.D., Department of Molecular Pharmacology and Experimental Therapeutics at the Mayo Clinic's Center for Individualized Medicine, who will develop and apply systems biology and network approaches to identify underlying regulatory mechanisms of tolerance from THoR data; Zoran Obradovic, Ph.D., the Laura H. Carnell Professor of Data Analytics, Director of the Center for Data Analytics and Biomedical Informatics, and Professor of Computer and Information Sciences at Temple University, who will develop predictive methods to characterize tolerance across multiple organisms; and Mike Levin, Ph.D., the Vannevar Bush Professor and Director of the Allen Discovery Center at Tufts and the Tufts University Center for Regenerative and Developmental Biology, who will investigate bioelectric mechanisms of tolerance and immune response and develop biophysical probes for characterizing tolerance in frog embryos.

Wyss Institute for Biologically Inspired Engineering at Harvard University
Kat J. McAlpine,, +1 617-432-8266


Seth Kroll,, +1 617-432-7758

The Wyss Institute for Biologically Inspired Engineering at Harvard University uses Nature's design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing that are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and formation of new startups. The Wyss Institute creates transformative technological breakthroughs by engaging in high risk research, and crosses disciplinary and institutional barriers, working as an alliance that includes Harvard's Schools of Medicine, Engineering, Arts & Sciences and Design, and in partnership with Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, Dana-Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Boston University, Tufts University, Charité - Universitätsmedizin Berlin, University of Zurich and Massachusetts Institute of Technology.

Wyss Institute for Biologically Inspired Engineering at Harvard

Related Engineering Articles:

Engineering a new cancer detection tool
E. coli may have potentially harmful effects but scientists in Australia have discovered this bacterium produces a toxin which binds to an unusual sugar that is part of carbohydrate structures present on cells not usually produced by healthy cells.
Engineering heart valves for the many
The Wyss Institute for Biologically Inspired Engineering and the University of Zurich announced today a cross-institutional team effort to generate a functional heart valve replacement with the capacity for repair, regeneration, and growth.
Geosciences-inspired engineering
The Mackenzie Dike Swarm and the roughly 120 other known giant dike swarms located across the planet may also provide useful information about efficient extraction of oil and natural gas in today's modern world.
Engineering success
Academically strong, low-income would-be engineers get the boost they need to complete their undergraduate degrees.
HKU Engineering Professor Ron Hui named a Fellow by the UK Royal Academy of Engineering
Professor Ron Hui, Chair Professor of Power Electronics and Philip Wong Wilson Wong Professor of Electrical Engineering at the University of Hong Kong, has been named a Fellow by the Royal Academy of Engineering, UK, one of the most prestigious national academies.
Engineering a better biofuel
The often-maligned E. coli bacteria has powerhouse potential: in the lab, it has the ability to crank out fuels, pharmaceuticals and other useful products at a rapid rate.
Pascali honored for contributions to engineering education
Raresh Pascali, instructional associate professor in the Mechanical Engineering Technology Program at the University of Houston, has been named the 2016 recipient of the Ross Kastor Educator Award.
Scaling up tissue engineering
A team at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A.
Engineering material magic
University of Utah engineers have discovered a new kind of 2-D semiconducting material for electronics that opens the door for much speedier computers and smartphones that also consume a lot less power.
Engineering academic elected a Fellow of the IEEE
A University of Bristol academic has been elected a Fellow of the world's largest and most prestigious professional association for the advancement of technology.

Related Engineering Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#530 Why Aren't We Dead Yet?
We only notice our immune systems when they aren't working properly, or when they're under attack. How does our immune system understand what bits of us are us, and what bits are invading germs and viruses? How different are human immune systems from the immune systems of other creatures? And is the immune system so often the target of sketchy medical advice? Those questions and more, this week in our conversation with author Idan Ben-Barak about his book "Why Aren't We Dead Yet?: The Survivor’s Guide to the Immune System".