'20 Years of Discovery' at ASU's Biodesign Institute: From the human microbiome to solutions for the developing world

Editor’s note: The Biodesign Institute at Arizona State University is celebrating its landmark 20th anniversary. This is the third installment in a series called “20 Years of Discovery.” Each story reflects on several groundbreaking scientific discoveries and impactful innovations made since the institute was founded in 2004.

The Biodesign Institute at Arizona State University, pioneered by visionary plant biologist Charles Arntzen, is an incubator for scientific breakthroughs — pushing the boundaries of what's possible in nature-inspired research and at the frontiers of bioscience. These innovations have reshaped our understanding of life and its workings and led to practical applications that have improved the human condition.

Here, we revisit several impactful and ingenious discoveries from a vast portfolio of research that embody the institute's commitment to creating a healthier and more sustainable future for all.

The human microbiome is comprised of trillions of microbes that inhabit our bodies and is a major research focus at the Biodesign Institute.

A pivotal study from the Biodesign Center for Health Through Microbiomes (2023) revealed the significant impact of diet on the gut microbiota and overall metabolic health. The study compares two diets: one high in fiber, resistant starch, and whole foods designed to nourish the gut microbiome — and a typical Western diet, high in processed foods.

Researchers discovered that the high-fiber diet, when compared with the Western diet, resulted in participants absorbing significantly fewer calories and having a greater amount of undigested food and higher bacterial biomass in their stools, implying that more energy from this diet contributed to expanding the gut microbial community. This research advances strategies to combat obesity and promote metabolic health through dietary adjustments.

Another study coming from the Biodesign Institute focuses on how the gut microbiome affects brain health, improving treatments and care related to autism spectrum disorder (ASD) and Pitt-Hopkins syndrome (2023). In groundbreaking clinical trials, researchers demonstrated that microbiota transplant therapy, which involves replacing harmful bacteria in the intestines with healthy bacteria, reduces gastrointestinal and other symptoms in people with autism, as well as in children with Pitt-Hopkins, a rare genetic disorder that causes physical and intellectual delays in development. The studies offer promising avenues for improving the quality of life for individuals affected by these conditions.

“Research at our center focusing on the gut and microbiomes are generating exciting insights into metabolism and the gut–brain connection,” says Rosa Krajmalnik-Brown, director of the Center for Health through Microbiomes. “This is important work that is relevant to human health and the treatment of a range of currently prevalent diseases and disorders.”

ASU researchers also investigated the transfer of bacteria and viruses from mother to baby at birth, which can impact the infant's long-term health (2020). The research underscores the critical role of microbial inheritance in shaping an infant’s future health prospects, including metabolism, immune-related health, and risks for conditions such as obesity and allergies.

The study reveals that, while a large portion of the infant's bacterial microbiome is inherited from the mother, the transfer of viruses is less straightforward and influenced by environmental factors. This research has implications for understanding infant health as it relates to conditions including asthma and autoimmune diseases.

Microbiomes also pervade the natural environment. Biodesign researchers study how land-based microbes contributed to seeding ancient seas with nitrogen (2018), a key nutrient. This research challenges the previous belief that early Earth's nitrogen cycle was primarily driven by oceanic microbes. It also highlights the significance of land-based biological soil crusts — composed of microbial communities like those in present-day deserts — in contributing to the nitrogen cycle during Earth's early history. This new perspective alters our understanding of Earth's early biogeochemistry and the role landmasses had in creating it.

In another microbiome study, researchers used a suburban solar farm in the lower Sonoran Desert to regenerate biocrusts (2023). Desert soil crusts, degraded by widespread human activity, are vital for erosion control, soil stabilization, nutrient cycling, water regulation and supporting desert biodiversity.

The research suggests that the shade provided by solar panels can create conditions conducive to the growth of these crusts, which may help to restore desert environments. This approach offers a dual benefit of renewable energy production and ecological restoration.

The Biodesign Institute is at the forefront of rapid advances in the field of structural biology, a branch of biology that focuses on the molecular structure of macromolecules like proteins, nucleic acids and complexes of these molecules.

The research involves exploring nature at the tiniest scales and briefest time intervals to unlock secrets of the molecular world. The findings play a crucial role in understanding processes ranging from how photosynthetic plants and organisms draw energy from sunlight to investigations of a broad range of cell receptors essential for leading-edge drug design.

Biodesign researchers have made groundbreaking discoveries using powerful new techniques including serial femtosecond crystallography (SFX) and cryo-electron microscopy (cryo-EM). These methods allow researchers to visualize the intricate 3D structures of proteins, receptors and other biomolecules with unprecedented detail.

Scientists used the SFX method to unveil the structure of the angiotensin receptor at an atomic level. The research team's results offer new insights into the subtle interactions between blood-pressure medications and their target molecules.   

Their findings help us understand how experimental drugs might regulate blood pressure, leading to better medications with fewer side effects, and potentially improve treatment for millions of people who must manage hypertension.

Another CXFEL study paves the way for a new generation of non-addictive painkillers (2015). Here, femtosecond X-ray crystallography was used to explore the structure of opioid receptors as they bind with their molecular targets.

By mapping the structure of these interactions, scientists can work on designing new analgesics that block pain without causing tolerance or dependency, a significant step forward in pain management.

In another major advance, SFX was used to determine the structure of NendoU, a key protein driving the spread the SARS-CoV-2 virus, cause of COVID-19 (2023). This stealthy protein helps the virus evade detection by the human immune system by modifying its RNA.

The high-resolution imaging provided insights into the protein's structure and dynamics, crucial for developing drugs that could allow the immune system to identify and target future dangerous variants of the virus.

ASU researchers made a significant breakthrough in identifying and analyzing structural details of Lyme arthritis, a debilitating illness associated with Lyme disease (2022). The team discovered that a protein on the Lyme bacterium forms pore-like structures, potentially acting as a gateway for disease-causing factors.

This finding, achieved through cryo-EM imaging, could lead to new drug treatments for Lyme arthritis, which affects 60% of untreated Lyme cases. The results open the door to effective treatments for this chronic Lyme disease complication.

Beyond human health, structural techniques are unveiling the inner workings of photosynthesis, unraveling how plants efficiently convert sunlight into chemical energy. This research on light-harvesting proteins could someday enable bio-inspired solar energy systems.

During these studies, researchers achieved a scientific milestone by capturing the first images of water splitting during photosynthesis, a process crucial for Earth's oxygen atmosphere. This breakthrough advances our understanding of how plants produce oxygen, paving the way for developing artificial photosynthesis.

“With our work at the center, we realize the dream of seeing biomolecules in action," says Petra Fromme, director of the Biodesign Center for Applied Structural Discovery. “Currently, most structural information only provides a static picture, but with the new time-resolved techniques we are able to detect the dynamics of molecules that are key to understanding the most important biological process on Earth like light conversion by photosynthesis. The molecular movies of proteins involved in human health will form the basis to develop novel drugs against diseases that plague humans, including infectious and metabolic diseases, cancer and neurodegenerative diseases.”

In a recent groundbreaking initiative, ASU researchers have begun creating the world’s first Compact X-ray Free Electron Laser, or CXFEL. The instrument is designed to transform structural biology, allowing detailed examination of biomolecular dynamics previously restricted to giant XFEL instruments, at the radically reduced scale of a laboratory benchtop. CXFEL’s applications are vast, including unraveling disease mechanisms at the atomic scale and developing new diagnostic imaging technologies.

To complete the development of this groundbreaking instrument, the U.S. National Science Foundation awarded the project a $91 million grant, marking the largest single research award in ASU's history (2023). 

The Biodesign Institute is pioneering a wide range of solutions to improve health and quality of life in the developing world, addressing environmental degradation, soil and water quality, and infectious diseases.

Scientists have introduced an improved breed of chicken called the Kuroiler to rural communities in Uganda (2011). Kuroilers, a hybrid chicken well suited for resource-poor environments, offer significant advantages over native chickens. The breed has already shown promise in India.

Key benefits of Kuroiler chickens include higher survival rates, increased meat and egg production, and improved income for rural poultry farmers. Kuroilers require no additional feed, as they can survive on agricultural and household waste. This initiative aligns with efforts to alleviate poverty and enhance nutritional security in rural areas. The hardy Kuroiler chickens also empower women tasked with raising chickens, improving economic freedom and providing much-needed dietary protein.

The Human Immunodeficiency Virus (HIV), the causative agent of AIDS, remains a deadly scourge. While anti-retroviral drugs have made AIDS a survivable disease, they are often cost prohibitive in resource-scarce regions.

The Biodesign Institute has promoted effective therapies for rural areas and pioneered advances in HIV vaccine development (2006). Despite the challenges, there is progress in understanding the immune response to HIV, with the first positive vaccine trial in Thailand indicating the potential for an effective vaccine.

The Biodesign Institute joined an international effort supported by the Bill and Melinda Gates Foundation to accelerate the development of an HIV vaccine. The initiative involves a collaboration with Switzerland's Lausanne University Hospital and a global consortium, using a $15.3 million grant to harness genetically engineered poxviruses in the fight against HIV/AIDS.

In the developing world, many HIV patients are also positive for tuberculosis. Fighting this lethal combination is a pressing medical concern. An ASU-led research team developed a rapid blood test to diagnose and measure the severity of active tuberculosis (TB) infections (2017). This NanoDisk-MS assay, a nanomedicine-based technology, detects minute levels of specific TB proteins in the blood.

The test, which delivers results in just hours, is more effective than current tests, especially for patients with HIV or TB in tissues other than the lungs, as those patients usually need biopsies. The test has a high accuracy rate for detecting TB in both lung and other body sites, regardless of HIV status. It also accurately differentiates between latent TB, other similar infections, and healthy individuals.

Dengue fever is a tropical disease spread by mosquitos and characterized by high fever, headaches and pain in muscles and joints. In serious cases, it can lead to severe bleeding, fluid in the lungs and organ failure.

Using molecular and cellular biology, researchers have worked to better understand four variants of the disease to aid efforts in developing a vaccine. Currently, there is no treatment for dengue.

“Understanding and fighting dengue with an interdisciplinary approach will allow us to tackle the disease at the population level (epidemiology, vaccination, policies), host level (infection, sickness, immunity) and cellular level (virus–cell interactions)," says Biodesign researcher Susan Holechek. “Partnering with other institutions from countries in which dengue is endemic provides us with a closer look into the dynamics of the disease while finding a global solution.”

Part of Holechek’s research involved extracting DNA from the Aedes aegypti mosquito to explore its genetic diversity. The study involved sampling in different geographic areas of Ecuador, where the dengue-carrying mosquito is prevalent.

Another infectious disease plaguing the developing world is caused by the Zika virus, which emerged as a global threat in 2015. In addition to potentially serious complications from the illness, the virus can be passed from pregnant mothers to their babies, resulting in devastating birth defects. Further, Zika patients often experience much more severe illness if they have previously been exposed to dengue.

Traditional diagnostic methods to accurately identify the disease have been inefficient and prohibitively expensive, particularly in the developing world where these technologies are needed most. Alex Green and his colleagues developed the first low-cost, paper-based diagnostic for Zika, requiring no sophisticated laboratory equipment or specialized training to administer.

The institute has also pioneered a Zika vaccine that can be produced at low cost. The strategy involves inducing tobacco plants to produce part of a crucial viral protein that allows Zika to cause infection. After creating sufficient material for the new vaccine candidate, Shawn Chen's team conducted immunization tests in mice. These tests induced both antibody and cellular immune responses, which were proven to provide complete protection against various strains of the Zika virus.

According to Josh LaBaer, executive director of the Biodesign Institute, “This is a great example of the brightest minds quickly coming together, with public support, to take on one of the most significant public health challenges of our time.”

Chen is a researcher with the Biodesign Center for Bioelectronics and Biosensors.