The Bioinformatics and Beyond Podcast

In this episode we focus on the applications side of synthetic biology for the environmental sciences and environmental microbiology with Dr. Ilenne Del Valle and Emm Fulk. To start, we walk through the more classical omics approaches for understanding environmental microbiology, setting us up for newer synthetic biology approaches. We then discuss the main questions in environmental microbiology that synbio is well suited to help answer. We discuss a few specific problems such as quorum sensing. We learn about what quorum sensing is and how synthetic biology can be used to help understand it.

Next we discuss how a researcher would conduct an environmental microbiology study using synthetic biology. We also briefly discuss ethical considerations for these topics, such as the ethics of releasing synthetically modified organisms into the environment as part of a study. This leads to an introduction on cell free sensors as yet another strategy for performing this type of work. We then hear about horizontal gene transfer as another phenomenon that synthetic biology can be used to better understand. We end with a discussion on cryptic processes that occur in microbial communities, how synthetic biology could allow for measuring these processes, and the overall role my guests see for synthetic biology in the future. For more on these topics, see Dr. Ilenne Del Valle and Emm Fulk's recent publication: https://www.frontiersin.org/articles/10.3389/fmicb.2020.618373/full

Dr. Ilenne Del Valle and Emm Fulk introduce the topic of synthetic biology in this episode. I start by asking, "What is synthetic biology?" We then begin digging into some of the intricacies of synthetic biology by learning about biosensors; biosensors are a fundamental component of synthetic biology for translating environmental inputs and outputs. We next talk about all the different molecules that biosensors can sense that we could use for various applications. 

Our conversation continues with introductions to many additional aspects of synthetic biology. We introduce and discuss synthetic biology circuit diagrams, which is another interesting area where the computational sciences and biological sciences converge. We next introduce CRISPR-based biosensors, synbio AND gates, and other logical operations that can used in the synthetic biology world. Finally, we discuss reporters. We introduce and cover several types of reporters and how they can help indicate which inputs are present. We end with a discussion of how synthetic biology components can be tuned to work even better, and the role bioinformatics can play in the world of synthetic biology.

This episode covers the review that both guests cowrote, that can be found here for further reading: https://www.frontiersin.org/articles/10.3389/fmicb.2020.618373/full

Dr. Kyle Frischkorn explains the interplay between different sample analysis methods such as transcriptomics and proteomics. He starts by explaining some of the basics of both transcriptomics and proteomics and gives a refresher on the central dogma. This explanation covers aspects of these methods such as a high level description of what they are, how they work, and what data you get from them. He also mentions more detailed considerations such as difficulties with mapping RNA back to genomes, the power of transcriptomes and metatranscriptomes, and different types of RNA sequencing that can be performed. 

We then move on to discuss Dr. Frischkorn's recent oceanography study. He starts by explaining the motivation behind this study. He explains the importance of understanding oceanography and the role of the ocean as a primary source for all chemistry that takes place on the planet, how the fixation of nitrogen is such an important part of the planet's chemistry, and how there are very few organisms that are able to turn nitrogen gas, which is highly abundant in the atmosphere, into biologically available nitrogen. He explains a further motivation which was to help resolve some of the unknown regarding if it is better to look at, for instance, transcriptomics or proteomics to perform these kinds of studies. We learn about how transcription and the presence of proteins might not necessarily always be totally correlated with one another. Finally, we do a deeper dive into the methodology of the study and learn how the study was performed, and conclude with some of the results and conclusions of what was found. We hear about the harmony and discord between transcriptomics and proteomics, and the "choreography" of the "dance" between these two methods. Dr. Frischkorn also explains a final, third piece of data that can be gathered, which is enzyme activity assays. The study discussed can be found at https://www.frontiersin.org/articles/10.3389/fmicb.2019.00330/full

In this episode, we attempt to take a look behind the machine of science with Nature Communications senior editor Dr. Kyle Frischkorn. We begin by simply asking the question, "How do you publish in Nature?" Dr. Frischkorn breaks down several of the main hurdles to getting published in Nature. These include having striking findings in the actual research and picking the right venue from within the Nature portfolio. We learn about different aspects that could potentially help or hurt your chances and where they fit into the publishing process. Topics include having a relationship with an editor, writing a cover letter, and working in a current hot topic of science. Dr. Frischkorn gives his thoughts on how an author might decide to submit to Nature, open access, and about the advantages and any potential disadvantages of publishing in Nature. Finally, we briefly discuss life as an editor. 

Dr. Leor Weinberger begins this episode by talking about his motivation for developing a novel therapy for HIV. He explains the fundamental mismatch between the mutation and transmission of the disease and how our therapies work, which inspired him to take a novel approach to try and combat the disease. 

We discuss topics such as the potential for scientists to give up on an HIV vaccine and why it seems like there are no good general antiviral drugs. To lead up to discussing Dr. Weinberger's new therapy, we hear a bit about the history of HIV therapeutics. After walking us through this history, culminating with the development and widespread adoption of the modern day drug cocktails for HIV patients, Dr. Weinberger introduces us to a fundamentally new type of therapy he has been working on to overcome previous barriers. He explains some of the origins of this new approach and explains how this approach is based on molecular parasites that steal resources from the virus. 

This new approach, which Dr. Weinberger refers to as therapeutic interfering particles, uses defective particles that function not by poisoning the virus but by stealing from the virus. He then explains how this approach overcomes the fundamental mismatch between HIV and HIV therapies. We hear some of the story of the long road from the initial idea for this work to the status of the therapy today. Dr. Weinberger also explains a sort of happy accident that happened in a petri dish that may have enabled this research to finally move forward.

Finally, we spend some time on the lower level mechanisms of how this therapy works, such as how you could deliver this treatment into a patient. We also talk about safety and the potential for public hesitancy. We conclude with a mention about the potential for this type of approach to be used for COVID-19 therapy.

Watch Dr. Weinberger's TED Talk on this topic at https://www.ted.com/talks/leor_weinberger_can_we_create_vaccines_that_mutate_and_spread?language=en

This episode begins by asking the question, "Why is it that we don't have an HIV vaccine after 40 years, but we do have a COVID-19 vaccine after one year?" Dr. Leor Weinberger explains that the answer to this question is primarily due to the existence (or lack thereof) of natural convalescents and whether the immune system is able to beat the virus. Dr. Weinberger further explains that there have only been two "recovered" people who had HIV. These two recoveries happened through bone marrow transplants, which themselves have 50 percent survival rates. Next, Dr. Weinberger gives a history of HIV vaccine development. Then, we drill down into the specifics of why HIV has been so challenging to develop a vaccine for. Dr. Weinberger explains the role of mutation as a primary source of this difficulty, coupled with the fact that HIV inserts itself into your genome and is able to persist in the body for decades, leading to no natural convalescents. 

To conclude, we hear Dr. Weinberger's thoughts on COVID-19 vaccine specifics such as how long COVID-19 may stay with us, if we may have to get additional vaccines, and how the persistence of antibody levels factors into these considerations. We end with a discussion on the mechanisms of the COVID-19 vaccines that have been developed. For those interested, a great resource for further reading on the bioinformatics of COVID-19 vaccine mRNA can be found at https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/

In this episode, Dr. Sabrina Green discusses the clinical aspects of phage use. We start by going back to one of the first ever uses of phage for a bacterial infection before discussing how phages are used now. Dr. Green explains a wide range of details related to clinical phage use. Topics discussed include cases today where phages are used, the safety of phages for clinical use, regulatory considerations for phage therapies, the pros and cons of phages, how specific phages are matched to specific patients, and phage affordability. Dr. Green describes potential hurdles for widespread adoption such as convincing people that viruses can be good for you. For further reading see https://www.liebertpub.com/doi/10.1089/phage.2020.0007 and https://mbio.asm.org/content/12/1/e03474-20

Dr. Zahi Fayad and Dr. Robert Hirten return to continue their discussion on wearable technology. This episode revolves around the study Dr. Fayad and Dr. Hirten performed to find out if wearable devices can identify and predict COVID-19. They discuss some of the struggles they had being “largely restricted in the data they could collect”. Their findings have the potential to be ground-breaking and showed “there are significant changes in your heart rate variability over 24 hours, which allows us to diagnose someone 7 days before a nasal swab”. To finish the episode, they discuss the potential to expand the study in the future, stating “The more you make these available to the researchers, the more helpful they will be to the healthcare biomedical research community”. Read more about their study at https://www.medrxiv.org/content/10.1101/2020.11.06.20226803v1.full-text

Dr. Zahi Fayad and Dr. Robert Hirten discuss all things wearable technology. Throughout the episode we learn about the exciting potential of this technology for conducting health studies and for the general wellbeing of the population. Dr. Fayad and Dr. Hirten explain what wearables do for athletes and for the general health of the public, even predicting “there is a market for the future for scaling it up and making it bespoke”. Dr. Fayad explains why he utilises many different wearables all at once, stating “I am competing against myself, it helps me stay motivated and helps me compete against myself everyday” when exercising. They then share their excitement with us on the future of wearables in human health. Finally, they finish off with a discussion on the uses of wearables in studies for such things as early heart attack warnings and COVID detection, with “almost all of them adding to their app the option to join a (COVID) study”. Dr. Fayad and Dr. Hirten will be returning in the next episode to discuss the exciting COVID-19 wearables work they’ve been doing!