The Bioinformatics and Beyond Podcast

In this second part of our history of metagenomics with Matthew Schechter, we start with a description of what a metagenome contains and how you analyze this type of data. Matt explains a few high level concepts such as metagenome assembly, metagenomic assembled genomes, contigs, contig binning, and genome completeness. Matt explains how metagenomics can help answer previously unanswered questions and even generate new hypotheses like in the example of the Candidate Phyla Radiation. Matt further explains how metagenomics is unbiased when compared to 16S sequencing and what his vision is for “Metagenomics 3.0.” Further topics discussed include pangenomics, further ways metagenomics can generate new hypotheses, and metapangenomics. Read Matt's full article of the history of metagenomics at https://merenlab.org/2020/07/27/history-of-metagenomics/

In this episode we begin our history of metagenomics with Matthew Schechter. Beginning with highlights like the initial ability to see microbes with a microscope and growing microbial colonies, we work our way through the history of metagenomics leading to modern day sequencing. Matt describes a discrepancy between culturing and what is present in a sample, and how sequencing began to overcome this discrepancy. Matt covers what 16S sequencing is and where it fits in the history of metagenomics. We end with a discussion of a seminal work on reconstructing genomes from sequenced metagenomes. Read Matt's full article of the history of metagenomics at https://merenlab.org/2020/07/27/history-of-metagenomics/

Dr. Heer Mehta starts by going over several of the ways that bacteria become resistant to antibiotics. Dr. Mehta explains the connection between specific antibiotics and specific drugs, and how she uses this information to know what to look for when studying the outcomes of experimental evolution studies. She explains how her group can isolate individual mutations that arise as a pathogen becomes resistant, and determine the difference in the protein structure caused by the mutation. We then discuss specifics of how Dr. Mehta and her group have studied the mechanisms for resistance used by individual pathogens, including a potential biosecurity threat. This discussion includes an example of a pathogen evolving resistance to two antibiotics in a single experimental evolution experiment. Finally, we discuss the potential uses for this type of research to translate to clinical usefulness.

Dr. Heer Mehta first goes over some basics of what antibiotic resistance is, why it is a global concern, and some related history. Dr. Mehta explains how bacteria are able to evolve to become resistant to antibiotics. She goes on further to explain how experimental evolution is one way scientists can understand this process and potentially use as a weapon in humanity’s battle against antibiotic resistant pathogens. She explains additional tools we can use such as microscopy and genome sequencing. We walk through how experimental evolution is setup, how the full experiment proceeds, and the final results that can be obtained. Additional topics discussed include pharmacodynamics and hypermutation.

We begin this episode by having Dr. Dinler Antunes explain what cancer immunotherapy is. Dr. Antunes gives an extremely thorough, clear explanation of what cancer immunotherapy is, how it works, and the many concepts involved. These concepts include how the human immune system works and how peptides are displayed on the outside of cancer cells. Further topics include how cancer cells can be differentiated from normal cells and the different types of immunotherapy possibilities that arise as a result. We then learn about some of Dr. Antunes own work, such as the HLA-Arena software package (see more at https://dinlerantunes.com/). Finally, we discuss the future promise and potential hurdles of cancer immunotherapy.

Dr. Dinler Antunes explains what the protein folding problem is and gives a bit of history on the problem. Dr. Antunes describes the types of methods for solving the problem computationally. He then discusses the rise of AlphaFold 2 for protein folding and gives his thoughts on its impact. Our discussion then shifts to the molecular docking and related problems, where the problem becomes to predict how molecules interact with each other. Dr. Antunes discusses how this problem shows up in the real world, for instance when a drug interacts with a protein. He explains the computational aspect of molecular docking and molecular dynamics. Finally, we learn about related work in relation to finding potential treatments for SARS-CoV-2.

Dr. Lauren Stadler describes the connection between environmental microbiology and bioinformatics. We start with an explanation of wastewater monitoring including how it is collected, cleaned, gotten rid of, monitored, and studied. Dr. Stadler defines and gives a bit of history on wastewater-based epidemiology. Dr. Stadler discusses how SARS-CoV-2 environmental monitoring could be widened and further developed to monitor other pathogens such as influenza. We then discuss the technical aspects of wastewater and environmental monitoring. Final topics include environmental monitoring after hurricane Harvey and engineering our drinking water. 

What if we could know how widespread COVID-19 is in our communities, in a low-cost way, that everyone automatically opts in to, with no additional effort? In this episode, Dr. Lauren Stadler tells us how her lab shifted from studying microbial communities in wastewater to monitoring levels of the SARS-CoV-2 virus in wastewater. Dr. Stadler explains how SARS-CoV-2 ends up in wastewater and how it can be used to track COVID-19 positivity rates. She discusses the incredible power and potential of this new form of community testing. For instance, she describes how the government is catching on to its power, the cost compared to individual testing, and how sequencing wastewater could give us additional information on how the virus is being transmitted. 

In this episode we revisit the “expanded” scientific skillset, discussing skills such as written and oral communication, marketing, people skills, listening, reading, networking, and literature search. Dr. Luay Nakhleh teaches us how to improve each of these skills. He explains how he continually asks himself, “How did I do?” He also explains how we can use this question to improve ourselves, in addition to feedback from others. Dr. Nakhleh then elaborates on further ways to improve skills. For instance, describing how our writing skills can be improved through a more mindful analysis of what we read. For each skill, Dr. Nakhleh attempts to define what it looks like to do that skill well. For instance, he addresses what it means to be a good listener and a good reader. Additional topics discussed include the role of social media in science and how to become an effective communicator when english is not your first language.

In this episode, we introduce and explore the “expanded” scientific skillset. Dr. Luay Nakhleh, who was recently named Dean of Engineering at Rice University, describes how communication is a requirement for leadership. He tells us the story of when he decided to grow his own communication skills, how he began improving, and the rewards of being an effective communicator. Additional skills such as marketing are discussed. For instance, Dr. Nakhleh explains how skillful marketing can help scientists spread their work and increase their impact. Further skills discussed include writing, listening, reading, people skills, networking, and literature review. For each of these skills, we attempt to highlight how they complement traditional career skills in STEM, why they are important, and how this importance can change depending on a person’s career goals.