Meet the Microbiologist Ashley Hagen, M.S.

Dr. Maria Eugenia Inda-Webb, Pew Postdoctoral Fellow working in the Synthetic Biology Center at MIT builds biosensors to diagnose and treat inflammatory disorders in the gut, like inflammatory bowel disease and celiac disease. She discusses how “wearables,” like diagnostic diapers and nursing pads could help monitor microbiome development to treat the diseases of tomorrow.
 
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Ashley's Biggest Takeaways Biosensors devices that engineer living organisms or biomolocules to detect and report the presence of certain biomarkers.   The device consists of a bioreceptor (bacteria) and a reporter (fluorescent protein or light). Inda-Webb’s lab recently published a paper in Nature about using biosensors (Sub-1.4 cm3 capsule) to detect inflammatory biomarkers in the gut. The work is focused on diagnosing and treating inflammatory bowel disease, but Inda-Webb acknowledged that that is a large research umbrella. The next step for this research is to monitor the use of the biosensor in humans to determine what chemical concentrations are biologically relevant and to show that it is safe for humans to ingest the device. It is believed that the gut microbiome in humans develops in the first 1000 days to 3 years of life. Early dysbiosis in the gut has been linked to disease in adulthood. However, we do not have a good way to monitor (and/or influence) microbiome development. Inda-Webb hopes to use biosensors in diapers (wearables) to monitor microbiome development and prevent common diseases in adulthood. In 2015, Inda-Webb became ASM’s first Agar Art Contest winner for her piece, “Harvest System.” Inda-Webb is the 2023 winner of the ASM Award for Early Career Environmental Research, which recognizes an early career investigator with distinguished research achievements that have improved our understanding of microbes in the environment, including aquatic, terrestrial and atmospheric settings. Learn More About ASM’s Awards Program Featured Quotes: We engineer bacteria to sense particular molecules of interest—what we call biomarkers—if they are associated with a disease. And then, we engineer a way that the bacteria will produce some kind of molecule that we can measure—what we call reporter—so that could be a fluorescent protein or light, like the one that we have in this device.

The issue is that inflammation in the gut is really very difficult to track. There are no real current technologies to do that. That is like a black box. And so, most of what we measure is what comes out from the gut, and has its limitations. It doesn't really represent the chemical environment that you have inside, especially in areas where you're inflamed. So, we really needed technologies to be able to open a window in these areas.

The final device that I am actually bringing here is a little pill that the patient would swallow and get into the gut. And then they engineer bacteria that the biosensors, will detect, let's say, nitrous oxide, which is a very transient molecule. And the bacteria are engineered to respond to that in some way—to communicate with the electronics that will wirelessly transmit to your cell phone. And from there, to the gastroenterologist.

We make the bacteria produce light. If they sense nitrous oxide, they produce light, the electronics read that, and the [information] finally gets into your phone.

Part of the challenge was that we needed to make the electronics very very tiny to be able to fit inside the capsule. And also, the amount of bacteria that we use also is only one microliter. And so, imagine one microliter of bacteria producing a tiny amount of light. Finally, the electronics need to be able to read it. So that has been also part of the challenge.

In this case, you have 4 different channels. One is a reference, and then the other 3 are the molecule of your choice. So, for example, what we show

Dr. Gary Procop, CEO of the American Board of pathology and professor of pathology at the Cleveland Clinic, Lerner School of Medicine discusses the importance of early detection and diagnosis in order to prevent fungal invasion leading to poor outcomes, particularly in immunocompromised patients. He emphasizes the importance of thinking fungus early, shares his passion for mentoring and talks about key updates in the recently released 7th Edition of Larone’s Medically Important Fungi.
Ashley's Biggest Takeaways Many invasive fungal infections are angiotrophic, meaning they actually grow toward, and into, blood vessels. Once the fungus has penetrated the blood vessel, the blood essentially clots, causing tissue downstream from the blood clot to die (infarction). When tissues that have been excised are viewed under the microscope, hyphal elements can be seen streaming toward or invading through the wall of the blood vessels. Once the clot forms, those hyphal elements can be seen in the center of the blood vessel where only blood should be. Antifungals cannot be delivered to areas where the blood supply has stopped. Therefore, treatment requires a combined surgical and medical approach, and the process is very invasive. Early detection can prevent these bad outcomes by allowing antifungal treatment to be administered before angioinvasion occurs. Links for the Episode: Expand your clinical mycology knowledge with the recently released 7th edition of Larone's Medically Important Fungi: A Guide to Identification. Written by a new team of authors, Lars F. Westblade, Eileen M. Burd, Shawn R. Lockhart and Gary W. Procop, this updated edition continues the legacy of excellence established by founding author, Davise H. Larone.
Since its first edition, this seminal text has been treasured by clinicians and medical laboratory scientists worldwide. The 7th edition carries forward the longstanding tradition of providing high-quality content to educate and support the identification of more than 150 of the most encountered fungi in clinical mycology laboratories.

Get your copy today with $1 flat rate shipping within the U.S. or order the e-book! ASM members enjoy 20% off at checkout using the member promo code. Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan.

From antifungal resistance to disaster microbiology and tales of visible mold growing across the skin of patients following a tornado in Joplin, Missouri, Dr. Shawn Lockhart, Senior Clinical Laboratory Advisor in the Mycotic Diseases Branch at the CDC talks all things fungi—complete with references to pop TV shows and the recently released 7th Edition of Larone’s Medically Important Fungi.
Links mentioned:
Larone's Medically Important Fungi: A Guide to Identification, 7th Edition (Use code: MCR20 at checkout for 20% off) CDC’s Mycotic Diseases Branch conducts an annual training course on the identification of pathogenic molds.  
 
 

Dr. Kate Howell, Associate Professor of Food Chemistry at the University of Melbourne, Australia discusses how microbes impact the flavor and aroma of food and beverages and shares how microbial interactions can be used to enhance nutritional properties of food and beverage sources.
Ashley's Biggest Takeaways Saccharomyces means sugar-loving fungus. Humans have similar olfactory structures and mechanisms as insects and are similarly attracted to fermenting or rotting fruits produced by Saccharomyces. Research has shown that insects (and humans) prefer yeasts that produce more esters and aromatic compounds. Palm wine is a product that is made from sap collected from palm trees (palm sap) across the tropical band of the world. Fruity flavors appear to be less important to persistence of Saccharomyces strains in an Indonesian palm wine fermentation. This may be because palm wine fermentation is very quick, generally 1-3 days often, with a maximum of 5 days for fermentation to be conducted. Wineries, on the other hand, ferment annually (one fermentation per year/vintage), when the grapes are right. Grape wine fermentations can take 7 days to 2 weeks to complete. So different selections likely take place between the 2 fermentation products. Featured Quotes: When we start drawing our lens on how microbes produce food for humans, we're coopting a process that happens quite naturally. Here I'll start off talking about Saccharomyces cerevisiae, the main fermenting yeast in food and beverage production, because it's one of the most studied organisms and was the first eukaryote to be sequenced.

Saccharomyces cerevisiae, as the name implies, loves sugar, and it flourishes when there's a lot of sugar in the environment. Where is sugar found? In fruits, and that's done quite deliberately, because fruits develop sugars and flavors and aromas to attract a birds or insects or anything else that can carry their seeds elsewhere for dispersal.

Now, Saccharomyces lies dormant in the environment in a spore before it encounters a sugar-loving environment. And then it replicates very quickly and tends to dominate fermentation. Humans have coopted that into our kitchens, into our meals, into our lives, and we use that process to produce food.

As Saccharomyces starts to use this sugar, it balances up its metabolism. And as it does this, it produces aromas. These aromas have a lot of important characteristics. Humans love them, but insects also love them too.

I've been interested in the yeasts that are found naturally in sourdough starters. Sourdough is a really interesting system. Because you've got yeast and bacteria interacting with one another.

One of the things we are collaborating on with colleagues in France at Inrae, Dr. Delphine Sicard, is to understand some of the non-Saccharomyces yeasts that are naturally occurring in sourdough starters. So here we're looking at a collection of a yeast called Kazachstania humilis and trying to understand how it has adapted to the sourdough environment, how its sustained over time and how different global populations differ to one another.

And this, of course, is of interest to the baking industry because not only do artisanal bakers have sort of an undiscovered wealth of biodiversity in their starters, baking companies also have an interest in using different sorts of flavors and bread for the commercial markets.

The connection between a chemical profile and a person’s sensory preference isn't something that's complete and direct. So, in every method that we use, there's always caveats, but we try to correlate it. Let's start off with the chemical characterization. We use headspace sampling, analytical chemistry, separation with gas chromatography and identification with mass spectrometry.

And we use different 2-dimensional methods to be able to understand what the very small compounds are, and to be able to identify them. We can semi-quantify these to be able to make comparis

Dr. Steve Diggle, ASM Distinguished Lecturer and Microbiology Professor at the Georgia Institute of Technology in Atlanta, Georgia and Dr. Freya Harrison, Associate Microbiology Professor at the University of Warwick in Coventry, U.K., discuss the science behind medieval medical treatments and the benefits of interdisciplinary research.
Ashley's Biggest Takeaways Diggle and Harrison met in Oxford, where Harrison was finishing up her Ph.D. and Diggle was doing background research for his work studying evolutionary questions about quorum sensing. When Diggle began searching for a postdoc, Harrison, who had been conducting an independent fellowship at Oxford and studying social evolution, applied. The AncientBiotics Consortium is a group of experts from the sciences, arts and humanities, who are digging through medieval medical books in hopes of finding ancient solutions to today’s growing threat of antibiotic resistance. The group’s first undertaking was recreation and investigation of the antimicrobial properties of an ancient eyesalve described in Bald’s Leechbook, one of the earliest known medical textbooks, which contains recipes for medications, salves and treatments. The consortium found that the eyesalve was capable of killing MRSA, a discovery that generated a lot of media attention and sparked expanded research efforts.   The group brought data scientists and mathematicians into the consortium (work driven by Dr. Erin Connelly from the University of Warwick). Together, the researchers began scouring early modern and medieval texts and turning them into databases. The goal? To mathematically data mine these recipes see which ingredients were very often or non-randomly combined in ancient medical remedies. The group recently published work showing synergistic antimicrobial effects of acetic acid and honey. They are also working to pull out the active compounds from Bald’s eyesalve and make a synthetic cocktail that could be added to a wound dressings. A 1,000-Year-Old Antimicrobial Remedy with Antistaphylococcal Activity. Medieval medicine: the return to maggots and leeches to treat ailments. A case study of the Ancientbiotics collaboration. Phase 1 safety trial of a natural product cocktail with antibacterial activity in human volunteers. Sweet and sour synergy: exploring the antibacterial and antibiofilm activity of acetic acid and vinegar combined with medical-grade honeys.
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Dr. Jessica Lee, scientist for the Space Biosciences Research Branch at NASA’s AIMS Research Center in Silicon Valley uses both wet-lab experimentation and computational modeling to understand what microbes really experience when they come to space with humans. She discusses space microbiology, food safety and microbial food production in space and the impacts of microgravity and extreme radiation when sending Saccharomyces cerevisiae to the moon.
Ashley's Biggest Takeaways Lee applied for her job at NASA in 2020. Prior to her current position, she completed 2 postdocs and spent time researching how microbes respond to stress at a population level and understanding diversity in microbial populations. She has a background in microbial ecology, evolution and bioinformatics. Model organisms are favored for space research because they reduce risk, maximize the science return and organisms that are well understood are more easily funded. Unsurprisingly, most space research does not actually take place in space, because it is difficult to experiment in space. Which means space conditions must be replicated on Earth. This may be accomplished using creative experimental designs in the wet-lab, as well as using computational modeling. Links for the Episode: Out of This World: Microbes in Space. Register for ASM Microbe 2023. Add “The Math of Microbes: Computational and Mathematical Modeling of Microbial Systems,” to your ASM Microbe agenda. Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan.