Modeling Zika virus transmission from mother to child using uterine mini-organs

Backed by Michelle E Moy, Papawee Nupason, Thida Wiwatpanit, Bunyarkrit Butchaiyar, Achara Nganthavee, Juthamas Udomsorayuth, Chayada & Colin Pearson, Chiara Franzoni, Yuwadee Talawanich, Janekrishna Kanatharana, and 91 other backers
$8,150
Pledged
101%
Funded
$8,000
Goal
2
Days Left
  • $8,150
    pledged
  • 101%
    funded
  • 2
    days left

About This Project

As of mid-2019, 87 countries have had or still have Zika cases, underlining the importance of this infectious disease. Zika virus can infect the uterus and later infect the infant during pregnancy, causing neurodevelopmental defects at birth. This study will model Zika infection in the lab using uterine mini-organs. We hypothesize that our specific antibodies can neutralize Zika virus in the uterus and thus prevent later transmission from pregnant mother to unborn child.

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What is the context of this research?

Researchers have discovered more evidence indicating that Zika infection during pregnancy can lead to newborns with neurological defects. In addition, with the specific mosquitoes carrying Zika endemic to Thailand and South East Asia, it is only a matter of time until Zika becomes an epidemic here. However, despite the increasing efforts to understand the mechanisms of Zika infection, we still do not have adequate ways to protect fetuses and infants from this infection. Our team is developing a strategy to prevent Zika virus transmission from pregnant mothers to their unborn child using specific antibodies. We hope that these new therapeutics can help lessen the devastating outcomes of Zika infection among infants in the affected regions worldwide.


What is the significance of this project?

Zika's problems among infants imposes significant financial and emotional costs to the family because it can transmit from infected pregnant mother to her unborn child, causing life-long developmental defects and intellectual disability. The affected child requires constant visits to the doctors, causing emotional and physical distress to both the child and their parents. The cost of proper healthcare for a child with birth defects is not something everyone can afford. The burdens to the affected family underscore the immediate need to develop effective means to prevent further mother-to-child transmission worldwide. The validation of our antibodies for Zika neutralization in the uterus will help put the field towards the development of therapeutics to stop the spread of Zika virus.

What are the goals of the project?

Our goal is to examine the efficacy of candidate therapeutics to neutralize Zika virus in the endometrium (the lining of the uterus) and block Zika transmission from mother to child during pregnancy. We need an initial fund to kickstart the project in order to obtain reliable results to apply for additional funding.

We will use uterine mini-organs (endometrial organoids) to model Zika viruses’ impact on the uterus (Wiwatpanit et al., 2019). With this system, we will examine the effects of Zika virus infection in the female reproductive tract and how we can neutralize the virus in uterine mini-organs. With the information and validation from this study, we can further strategize how to prevent Zika's later transmission from the uterus to the infants.

Budget

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We are asking for $8,000 for this project. We will generate uterine organoids using biopsies from volunteers already undergoing hysterectomy. We will grow them in conditions mimicking the local cellular environment. We will test these organoids for their identity and functions to confirm that they behave like the real organ. The majority of funds will go towards this crucial step.

We will infect the organoids with Thai patient-isolated Zika viruses and measure the level of infection at different stages to determine the basis of Zika infection. We will then treat them with Zika-neutralizing antibodies. We expect that they would eliminate Zika in the uterine organoids and prevent further transmission.

Your support is critical for us to kickoff and get preliminary data to secure additional funding to expand the project. Ultimately, we will build a multi-organ platform to understand how Zika virus can pass from mother to infant, and how to stop this process entirely.

Endorsed by

Zika virus is still an important threat. The infection is still endemic in the Southeast Asian and many other regions. The placental model will not only enable testing of the exciting monoclonal antibody, but will also provide us with more insight into the mechanism by which the virus is transmitted from mother to fetus. At Siriraj, we believe in translating new knowledge to the benefit of mankind and I am really excited that our researchers work on this important project.
This is a terrific research project that addresses a compelling topic. Dr. Wiwatpanit and his team are uniquely well-qualified to organize this study. This has a strong link to improving health in Thailand.
This project is very relevant to the need of countries threatened by Zika virus, including Thailand and other developing countries. His proposal to use antibodies to stop mother-to-child transmission of the disease is a potential straightforward solution and can be tested by using organoids derived from the uterus, a technique in which he is specially suited from his previous experience. He is a young dynamic researcher with unique expertise suited to answer new challenges posed by this disease.
I enthusiastically endorse Tee and his team with expertise in bioengineering, virology, virus genetics and obstetrics and gynecology. This study is an innovative response to Zika epidemics and its devastating effect on children and their families. Using endometrial organoid to study virus neutralization with blocking antibodies is a ground-breaking model to examine a strategy to prevent Zika transmission from pregnant women to the fetus. Let´s support Tee and contribute to the development of preliminary data needed to expand this project!

Flag iconProject Timeline

We are aiming to establish a uterine mini-organ system permissible to Zika infection within the first year. We estimate that by the end of the second year, we will be able to determine the extent of Zika neutralization of our specific antibody. For the next step, we will use the data from this study to strategize how we can use these antibodies to block Zika later transmission from the uterus to the fetus by bioengineering a system to study the placenta in the lab.

Mar 30, 2020

IRB application + Human Ethics Guideline submitted

Aug 30, 2020

IRB approval granted

Oct 15, 2020

Project Launched

Nov 30, 2020

Laboratory supplies and reagents procured

Dec 31, 2020

Organoid system generated and validated

Meet the Team

Teerawat Wiwatpanit
Teerawat Wiwatpanit
Researcher

Affiliates

Frontier Biodesign and Biomolecular Engineering Research Team, National Center for Genetic Engineering and Biotechnology, Thailand
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Bunpote Siridechadilok
Bunpote Siridechadilok
Senior Researcher

Affiliates

Frontier Biodesign and Biomolecular Engineering Research Team,National Center for Genetic Engineering and Biotechnology, Thailand
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Team Bio

Bioengineer:
Teerawat Wiwatpanit, PhD

BIOTEC, Thailand

Genetic virologist:
Bunpote Siridechadilok, PhD

BIOTEC, Thailand

Ob/Gyn Surgeon:
Suwanit Therasakvichya, MD

Obstetrics and Gynecology Department,

Faculty of Medicine Siriraj Hospital, Thailand

Virologist and Immunologist:
Juthathip Mongkolsapaya, DPhil(Oxon)

Dengue Hemorrhagic Fever Research Unit,
Faculty of Medicine Siriraj Hospital, Thailand
Nuffield Department of Medicine, University of Oxford, Oxford, UK

Teerawat Wiwatpanit

I am originally from the Northern part of Thailand. I did my undergraduate training in Biology and Visual arts at Bowdoin College in Brunswick, Maine. In 2011, I started my graduate training in Life Sciences at Northwestern University in the heart of Chicago, Illinois, and later remained there for my post-doctoral training at the Department of Obstetrics and Gynecology. While there, I was a part of the team of scientists that developed a multi-organ culture model for the female reproductive tract that allowed for disease modeling and high throughput drug testing. Just this April 2019, I returned to Thailand and joined the National Center for Genetic Engineering and Biotechnologyat Thailand Science Park—the largest fully-integrated R&D hub in Thailand—to integrate my scientific expertise.

My specific interests lie in utilizing tissue engineering techniques to generate experimental models that will continue to evolve our understanding of the genetics and pathogenesis of human diseases. Within the framework of my expertise in organoid culture and tissue engineering, I hope to advance the field of precision medicine allowing it to be both highly effective in identifying and treating diseases in a more accessible manner in the near future. In addition, having been a collaborative member of Northwestern’s Department of Obstetrics and Gynecology, I have come to appreciate the importance of women’s health through increasing the quality of health information available as well as healthcare specifically catered for women.

Bunpote Siridechadilok

I am from Bangkok. I did my undergraduate at Brown University and my Ph.D. at UC Berkeley. I am a molecular biologist who has been working on dengue and Zika viruses. My research group has been focusing on developing and applying techniques to genetically dissect dengue and Zika viruses to better understand how viruses counter host immune system, are transmit in mosquitoes, and replicate in cells, with the aim of utilizing the genetic information to develop effective live-attenuated vaccine. I am currently working at the National Center for Genetic Engineering and Biotechnology (BIOTEC) at Thailand Science Park and am also a part of a dengue research network that involves BIOTEC, Thailand; Mahidol University, Thailand; and Oxford University, England.

Additional Information

Crowdfunding for Science

With more and more constraints on scientific funding worldwide,
researchers are having a difficult time securing supports for their
work, especially among those relative early in their career like PhD
students, postdoctoral fellows or young principal investigators.
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SESH Global

Just like crowdfunding for business, crowdfunding for researches allows scientists to connect with the people they are helping. With the
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To give back to your backers, you, the science guys, are updating them
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Everything counts.



TDR, partnered with SESH Global, aims to build capacity for crowdfunds among researches from low- and middle-income countries studying infectious diseases.

Crowdfunding is a relatively new and unexplored territory for scientific
research communities. TDR, the Special Programme for Research and Training in Tropical Diseases, at World Health Organization recognizes this as a great opportunity to help researchers fund their projects given the increasing
difficulties to secure research funding. Our project on "Blocking Zika
Virus Mother-to-Child Transmission" won this year's TDR crowdfunding
challenge. For this project, we will be using a new and innovative
tissue engineering technique to study the biology of Zika virus and how
it can pass from pregnant mother to her fetus. With your help through
crowdfunding, we will develop a way to block this transmission to
prevent the child from Zika-related complications such as microcephaly.

More information on our mission and fun posts from our lab please visit our blog at

https://busymosquitoes.blogspot.com/


Battle Against Zika

Zika Virus

With the rapid spread of Zika virus infection and the strong
correlation between Zika virus infection among pregnant mothers and later microcephaly cases among their newborns (underdeveloped brain upon birth), World HealthOrganization (WHO) declared Zika a Public Health Emergency of International Concern regarding microcephaly and Zika infection in early 2016. While WHO announced that Zika was no longer a global "emergency", the risk assessment of Zika is still the same. The real meaning of it all is worse as this means Zika is here to stay, and we need a long-term strategy to control Zika virus infection.


The Threat

Zika virus can spread through specific species of mosquitoes, and from infected mother to her unborn child. While Zika virus infection symptoms are mild, if any, in adults, it is no confirmed that Zika virus infection during pregnancy can cause severe brain damages in newborns and even death.

Zika virus infection is health and socioeconomic problems. The affected child needs constant check-ups with healthcare providers throughout their life. The cost of proper cares for a child with birth defects can add up to millions of dollars throughout their life time—sadly a cost that not every family can afford.

Infant affected by Zika-related microcephaly. Diego Herculano/Brazil Photo Press/Latincontent

The Solutions

Mosquito control programs worldwide can help slow down the spread of Zika virus. But, that is not enough. At the moment, there is no effective drugs or vaccines to protect the fetuses. That is where we come in, we are trying to develop a way to prevent the spread of Zika virus from pregnant mother to her unborn child. Our bioengineering team is developing a cell culture model to understand how Zika virus can pass from pregnant mother to her unborn child. With this model, we can further test our anti-Zika factors to see if they can block its transmission.

We would like to reach out and raise awareness of the real danger of Zika virus. We are inviting you to be a part of our mission to combat Zika viruses. We hope that you guys are as SUPER excited about developing drugs that can block Zika virus transmission, and ending its threats among children once and for all.

More information on our mission and fun posts from our lab please visit our blog at

https://busymosquitoes.blogspot.com/



Project Backers

  • 129Backers
  • 101%Funded
  • $8,150Total Donations
  • $63.18Average Donation
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