Prion Diseases, a New Paradigm of Infectious Agents

Once considered heretical, prions are now known to be comprised of only protein. First supported by a series of experiments correlating PrPSc, the prion conformation of the normal host protein PrPC, with prion infectivity, recent experiments have synthetically generated infectious prions from minimal components. Synthetic prions cause bona fide prion disease in animals that also replicate PrPSc fulfilling Koch’s hypothesis. This new paradigm of infectious agents has implications for other protein-misfolding diseases such as Alzheimer’s disease and Parkinson’s disease.

Prion Strain Biology: How Does a Protein-Only Infectious Agent Encode Information?

Prions are comprised of PrPSc, a misfolded form of the cellular host prion protein, PrPC. Within a given host species, distinct strains of prions are characterized by differences in incubation period, distribution of PrPSc within a host and zoonotic potential. A significant hurdle for the prion hypothesis was providing a mechanism for how a protein-only infection agent could encode strain diversity and perform complex biological functions. Recent compelling evidence now indicates that prion strain diversity is encoded in distinct strain-specific conformations of PrPSc.

Environmental Fate and Persistence of Prions

Prions are comprised solely of protein and, as such, are unusually resistant to inactivation and can persist in the environment for decades. Recent evidence suggests that the interaction of prions with soil, in combination with the hydration state of the particle, may protect prions from the impact of weathering. These prion soil interactions are dictated by the matrix that prions enter the environment and may also aid in the bioavailability of prions to infect a new host. Recent studies are investigating means of detecting prions in the environment and developing mitigation procedures to try to slow the spread of deadly prion diseases.

Prions and Prion-Like Diseases of Humans

Prions are comprised of PrPSc, a misfolded form of the cellular host prion protein, PrPC, and are characterized by long subclinical incubation periods followed by the onset of neurological disfunction. Over the last decade, it is becoming increasingly clear that other protein misfolding neurodegenerative diseases (e.g., Alzheimer’s, Parkinson’s) share many features with prion diseases. These commonalities include (i) biochemically similar process of formation of the misfolded form of the normal host protein, (ii) similar pattern of transsynaptic spread within the central nervous system, (iii) injection of the misfolded form of the protein in a susceptible causes disease and (iv) distinct biochemical properties of the misfolded form of the protein correlate with distinct clinical and neuropathological features of disease, reminiscent of prion strains. While evidence is mounting for similarities of these diseases, it is a highly controversial topic with far reaching implications.

Chronic Wasting Disease, an Emerging Prion Disease of Cervids

Chronic wasting disease (CWD) in an emerging inevitably fatal prion disease of cervids that has been described as an existential threat to wild cervids. CWD is highly contagious and can reach incidence rates of over 50% of animals in a given population. The geographical range of CWD is expanding in North America and has recently been identified in Scandinavia. While it is known that prions can be zoonotic (e.g., mad cow disease infection of humans), the host range of CWD is poorly described and conflicting evidence exists for the risk of transmission of CWD to humans.

In addition to providing lectures for branch meetings, ASMDL lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Judge posters and/or oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.

The Bacterial Protein Export Zoo

All bacteria have pathways for exporting specific subsets of proteins from their site of synthesis in the bacterial cytoplasm to the cell envelope or extracellular environment, where exported proteins play critical roles in bacterial physiology and pathogenesis. There are many types of protein export systems, and new systems are being discovered all the time. This lecture will discuss different pathways that bacteria use to solve the problem of exporting proteins across permeability barriers. Functional similarities between diverse systems will be highlighted, including examples of components that are shared between or co-opted from different systems.

Survival in the Belly of the Beast: Bacterial Survival Strategies in Macrophages  

There are many examples of bacterial pathogens that survive in the normally hostile environment of the macrophage. Such intracellular bacteria have mechanisms, which commonly involve secreted bacterial effector proteins, to resist the antimicrobial attack or subvert the innate immune response of macrophages. There is often a high level of redundancy incorporated into these mechanisms to ensure bacterial intracellular survival. This lecture will discuss similarities and differences in mechanisms used by an array of intracellular pathogens, including Mycobacterium tuberculosis.  

TB or Not TB? That Is the Lecture.

Mycobacterium tuberculosis, the infamous bacterial pathogen responsible for tuberculosis, remains a significant global health problem, accounting for 1.5 million deaths per year. In addition to M. tuberculosis, there are pathogenic nontuberculous mycobacteria (NTM) that are a growing threat, particularly for individuals living with cystic fibrosis or chronic obstructive pulmonary disease. Mycobacterium abscessus, a NTM found in soil and water, is among the most common NTMs encountered in NTM pulmonary disease, and it is highly drug resistant. M. tuberculosis and NTM pathogens share many similarities, including the ability to survive in macrophages and to induce the formation of granulomas. However, there are also differences between these mycobacterial pathogens that need to be understood to inform therapeutic development. This lecture will compare and contrast tuberculous and nontuberculous mycobacteria and their associated diseases.

In addition to providing lectures for branch meetings, ASMDL lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Judge posters and/or oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.

Molecular Mechanisms of Environmental Stress Resistance in Bacteria  

Our lab seeks to understand molecular mechanisms that underlie the ability of bacterial cells to survive in complex, dynamic environments, including mammalian hosts. To this end, we utilize an interdisciplinary set of genetic, biochemical, biophysical and computational approaches to address these questions on multiple scales, from the cellular/systems level to the level of molecular structure. Our most recent work in this area includes the discovery of novel bile resistance genes in the opportunistic gut pathogen Bacteroides fragilis and dissection of a multicomponent sensory system that is critical for Brucella infection of its mammalian hosts.  
 

Using Environmental Cultivation Approaches to Understand Gene Function in Ecosystems Contexts  

The ability of bacterial cells to execute complex processes in their environment is directly determined by the proteins and RNAs encoded within their genomes. Genomics research programs have cataloged millions of bacterial genes and the 3D structures of thousands of proteins. However, data that define the cellular functions of uncharacterized genes and proteins in these large datasets have been slow to emerge. Indeed, nearly 1/4 of cataloged protein domain families lack any annotated function. To address this problem, we have developed a workflow that combines modern mutagenesis and DNA sequencing methods with environmental cultivation approaches that favor ecological and geochemical complexity over standard laboratory media. Our initial studies in this area have defined genes that are required for Caulobacter crescentus growth and survival in the natural waters of inland Michigan lakes and the Great Lakes. 

In addition to providing lectures for branch meetings, ASMDL lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Judge posters and/or oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.
• Participate in roundtable discussions with microbiologists from a variety of sectors, including clinical labs, biotechnology industry, academic labs, primarily undergrad teaching institutions, law, etc. 
• Participate in short (e.g., half-day) technical workshops; I have expertise in structural biology and genomics and would be willing to participate in workshops in these areas.

What Can Large-Scale Comparative Genomics Teach Us: The Use of Machine Learning to Identify Bacterial Virulence and Tropism Genes  

Our realization of the near universality of horizontal gene transfer (HGT) processes among bacteria, combined with the observation that HGT could serve as a population-level virulence factor, led to the genesis of the distributed genome hypothesis and, consequently, to the pan-genome concept. The testing of these new paradigms required us to develop large-scale genomic technologies (next-generation sequencing and comparative genomic software) to be able to characterize and compare large numbers of genomes from within multiple bacterial species. From these studies we determined that all bacterial strains within species contained a common core genome, but each strain contained a unique subset of genes that were variously “distributed” among the component strains. The near-universal finding that the number of distributed genes per species was far greater than the number of core genes led us to the first application of statistical genetics and, later, machine learning approaches to identify, in an unbiased manner, unannotated genes from the genomic dark matter that were associated with infection, virulence and tropism. This approach has provided a directed means to uncover novel biology underlying a trait of interest. 

Development and Use of Microbial Trans-Pan-Domain Assays as Universal Species-Specific Molecular Diagnostics  

The quest for an unbiased, universal DNA diagnostic, which could be used to characterize any specimen for any and all cellular microbes has been the “holy grail” of PCR jockeys for 35 years. To bring this concept to fruition, we have exploited long PCR and long-read circular consensus sequencing (CCS) to develop and validate a pair of pan-domain microbiome assays. In the first case, we target the entirety (~1,400 bases) of the bacterial 16S gene, and in the second case, we target a >3-kb fragment of the eukaryotic ribosomal operon. When combined, these assays provide for a semiquantitative microbial trans-pan-domain molecular diagnostic that provides near-linear results for species spread over 4 orders of magnitude in the same specimen. The combination of the long-read sequencing and the single-molecule error correction provided by the CCS provides for species specificity throughout the entire bacterial, fungal and single-celled parasitic domains of life. Applications of these assays have produced findings as diverse as identifying previously unknown bacteria as biomarkers for specific cancers, brain-specific microbiomes associated with Alzheimer's disease and differences in tick microbiomes based on geo-spatial sampling.  

Bacterial Biofilms as Multicellular Pathogens  

How do chronic bacterial pathogens persist in the face of antimicrobial therapy, as well as the innate and adaptive host responses? To understand this complex phenomenon, we promulgated the rubric of “bacterial plurality,” which embodies the concept that bacterial biofilms are multicellular organisms that display enormous heterogeneity at many levels, including phenotypic, metabolic and genotypic. The reasoning behind the development of this theoretical construct was to provide a paradigm that more accurately models chronic pathogenic processes, enabling the development of rational therapies for these diseases that are recalcitrant to current medical management. We hypothesized that the extant paradigms of bacterial pathogenesis passed down to us from Robert Koch and developed for acute epidemic infections, although powerful and useful for clonal planktonic infections, acted for decades as blinders to our understanding of chronic infections. As part of our studies of bacterial plurality, we have participated in the development of a new understanding of bacterial ecology, which includes the realization that bacteria have a developmental life cycle, can exist as solitary organisms or as part of a complex interacting multicellular community, and can phenotypically adapt to changing environmental conditions. Phenotypic heterogeneity is explained by the fact that nearly all bacteria can form biofilms or even more complex large-scale structures for protection, generation of reducing power and dispersal. Metabolic heterogeneity results (in part) from the understanding of limiting nutrient fluxes into a biofilm and the bacteria's responses to those fluxes, including the triggering of the stringent response, which renders the bacteria metabolically resistant to antibiotic therapy while also upregulating their virulence mechanisms. 

Defanging Pathogens: Development of Antivirulence Drugs  

Antibiotic resistance has been a recognized and growing problem for more than 50 years. Yet despite repeated exhortations to act from multiple national and international health organizations, the problem has become increasingly exacerbated over the decades. This is largely due to the design of antibiotics to kill the offending microbes, thus supplying enormous selective pressure for them to become resistant. To address this issue, we have begun a program to develop drugs that inhibit virulence gene expression, whereby we “defang” the pathogens and return them to a commensal state as opposed to killing them. We are currently characterizing a compound that inhibits virulence factor production in both a major gram-negative pathogen (Pseudomonas aeruginosa) and a major gram-positive pathogen (Staphylococcus aureus).

In addition to providing lectures for branch meetings, ASMDL lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Judge posters and/or oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.
• Hold a session on career development—focusing on the intangibles.

Chlamydia Is a Master Cell Biologist 

Chlamydia is an obligate intracellular bacteria that creates a specialized niche to survive within the hostile environment of the host cell. To do this, it secretes over 100 effectors into the host cell to reprogram host cell biology. In this lecture, I describe how we have used a multidisciplinary approach, including proteomics, cell biology, bacterial and host cell genetics and structural biology to begin to unravel how Chlamydia hijacks host processes.

Pathogenesis of Pseudomonas aeruginosa Infections With a Special Emphasis on Bacterial Signal Transduction, Virulence Programs, Secreted Effectors

In this lecture, I describe how a clever genetic screen, performed over 25 years ago, has given insights into how this bacterium activates a virulence program upon surface contact to avoid being eaten by its natural or host predatory cells. I will describe how the bacteria responds to surface contact, the signal transduction system used and what the consequences of activating an acute virulence program are. I will then relate this system to human infections.

Bacterial Adaptation—A Short Term Memory System 

In this lecture, I review how adaptation works in bacterial signaling systems, from chemotaxis to surface sensing systems. 

Bacterial Mimicry of Viruses 

In this lecture, I will introduce the idea of short linear motifs, a strategy used by viruses and bacteria to mimic or hijack host protein-protein interaction surfaces to reprogram host processes.  

In addition to providing lectures for branch meetings, ASMDL lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.

How Novel Receptors Arise in Bacteria

Chemoreceptors provide bacteria with an opportunity to detect numerous signals in the environment and to navigate towards favorable conditions. The number of chemoreceptors in bacteria varies significantly—from just a few to more than 50—and different bacterial species evolved unique receptor proteins. Where do these novel receptors come from? We will discuss how gene duplication serves as a foundation for evolving receptors with novel sensing capabilities. We will also consider other, unique mechanisms for how new receptors are born to enable bacteria to better adapt to their environment.

Amino Acid Sensor Conserved from Bacteria to Humans

Amino acids are building blocks of life. They serve as nutrients and as signaling molecules. Thus, it is critical for all living cells to be able to detect the presence of amino acids in their surroundings. Bacteria, archaea and eukaryotes evolved various receptors capable of sensing the presence of amino acids and different ways of amino acid binding by these receptors. However, no universal mechanism of amino acid sensing is currently known. This talk will reveal how amino acids are detected by the most ubiquitous bacterial sensor and how this sensor was transferred to archaea and eukaryotes, including humans, where it serves an important role in neurotransmission.

Signal Transduction in Bacteria: Mix-and-Match of “LEGO Bricks”

Bacteria adapt to changing environmental conditions by adjusting their cellular functions— from motility to gene expression. These adjustments are mediated by signal transduction systems that have a modular design. Like famous LEGO construction toys, bacterial signal transduction systems are based on a nearly endless combinatorial possibility of constructing objects by using simple “building bricks”– protein domains. As in the LEGO game, some “bricks” are used in bacterial signal transduction very often, whereas other, more unique shapes are used rarely, only on certain occasions. This talk will introduce the audience to this bacterial LEGO game: from simple shapes to complex compositions of bacterial signaling schemes.

Bacterial Signal Transduction in Various Environments and in the Human Microbiome

Signal transduction systems in bacteria link environmental signals with appropriate cellular responses. Various bacteria occupy drastically different ecological niches, which raises a question: does the environment affect signal transduction in bacteria? We will discuss how bacteria from oceans differ from soil bacteria in their ability to sense their environment. Similar trends will then be revealed in the human microbiome: bacteria from the oral cavity differ from the gut-inhabiting bacteria in terms of how many genes they dedicate to sense their surroundings. We will further explore how understanding signal transduction in beneficial gut bacteria can help in designing future antibiotics to fight pathogens.

In addition to providing lectures for branch meetings, ASMDL lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Judge posters and/or oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.

Antimicrobial Resistance Initiatives—Do They Work?  

In an effort to increase antimicrobial drug discovery efforts, a focus on medical needs to combat antibiotic resistance is becoming more prominent. Multiple initiatives from both the public and private sector have been proposed. This lecture provides personal experience with approaches that have worked in the past, followed by proposed initiatives that may be useful in the future. 

How Can We Motivate the Pharmaceutical Industry to Invest in Antimicrobial R&D?  

The pharmaceutical industry has backed away from antibacterial research and development in the past few years. Creative approaches that result in commercially viable products are necessary to re-energize this industry. Both science-based and business-related considerations must be included in the discussions. 

Novel Approaches to Antibacterial Drug Development Are in Your Future  

With the continuing and increasing threat of antimicrobial resistance, novel approaches to new agents are required. In the future, small-molecule antibiotics will share the therapeutic platform for infectious disease with biologics, bacteriophages and agents that affect the microbiome. Novel therapies that will not share resistance mechanisms with current drugs are currently being developed. Their success will be judged as new resistant pathogens emerge in the future.    

Navigating a Career Path as a Microbiologist  

There are so many amazing career choices for microbiologists, spanning nearly the entire spectrum of sectors, organization types, roles and geographies. How does one decide where to start, what to look for in an organization, how to capitalize on your network or how to know when to shift gears? The stories of personal journeys and experience from the perspective of an industry leader will frame the discussion. 

Understanding the Biotech and Pharmaceutical Industry Partnership Environment  

When exciting science is emerging from the bench, what is critically important from an investor or research and development (R&D) partner perspective? What are some of the aspects of one’s scientific and business approach that require special attention when pitching to investors, potential partners and top talent? The experience as a big pharma science and business partner, both on the buying and selling sides, as an investor, as a board member and as a start-up advisor will frame the discussion. 

In addition to providing lectures for branch meetings, ASMDL lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL lecturer has indicated interest in doing the following:

• Judge posters and/or oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.
• Other: "I'm open to other ways that I can contribute."

A Virus Is a Community

This lecture introduces students to the concept of a virus as a community of particles with distinct genomic composition and functions. In addition to the parental standard viral genome, various other non-standard forms of the viral genome are generated as the virus replicates, providing essential functions and altering the outcome of viral infections. We go through specific examples of well-characterized non-standard viral genomes and their role during infection.

Antiviral Immunity, Interferons and the Host-Virus Struggle

In this lecture I provide an historical perspective on the discovery of interferons, which are the primary antiviral molecules, and walk the audience through the state of the field to date. We discuss how viruses that are adapted to the host block or interfere with the action of interferons and how, ultimately, the virus is controlled upon the emergence of highly immunostimulatory non-standard viral genomes.

A Division of Labor During Virus Infections

In this lecture we discuss concrete examples of how different components of the viral community differentially impact infected cells. While some cells are dominated by the standard virus and function as a virus producing machine, others are dominated by non-standard viral genomes and are engaged in the production of cytokines that will initiate the antiviral response. These antiviral cells also survive the infection longer, allowing for the persistence of a virus reservoir. Understanding how each of the components of a virus interact and impact the host organism is essential to come up with innovative ways to control virus infections.

In addition to providing lectures for branch meetings, ASMDL lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.

Exploring the Dark Matter of Phage Genomes

While there is greatly renewed interest in the use of phage therapy to treat human infections in response to rapidly increasing rates of antibiotic resistance, phages are known to transmit bacterial virulence factors and contribute to immune evasion. As the functions of most phage genes remain unknown, it is currently very difficult to predict potential complications that may arise during treatment. This lecture outlines ongoing efforts to determine the biological functions of genes comprising the “dark matter” of phage genomes, which will allow us to engineer phages with increased efficacy and safety.

Chemical Defense in the Phage-Host Evolutionary Arms Race

Bacteria use small chemical molecules for a variety of purposes, including cell-cell communication, upregulating cellular processes in response to environmental stimuli and inhibiting the growth of competing organisms that share the same environment. This lecture covers recent work that shows that bacteria use small molecules directly to protect themselves from phage predation, as well as indirectly via quorum sensing pathways to regulate anti-phage defenses and warn surrounding cells of the danger of infection.

Off-switches for CRISPR-Cas9: From Phage Biology to Biotechnology

CRISPR-Cas systems provide bacteria with adaptive immunity that protects them from phage predation. In response to this evolutionary pressure, phages have evolved protein inhibitors, known as anti-CRISPR proteins, that allow them to overcome CRISPR-Cas immunity. This lecture discusses how these proteins function in bacterial cells to inhibit CRISPR-Cas systems and allow phage replication, as well as their biotechnological uses in genome editing and gene drive applications.

In addition to providing lectures for branch meetings, ASMDL Lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL Lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Judge posters and/or oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.

Antibiotic Discovery from a Single Bacterial Colony  

This lecture will detail efforts to collect environmental bacteria from around the globe for use in new antibiotic discovery. In particular, novel methodologies to grow, identify and analyze the antibiotic-producing capacity of bacteria will be presented. The lecture will culminate in the discovery and identification of a new antibiotic from a bacterium collected between continental shelves in Iceland.  

Rethinking Microbial STEM Education: A University-Community Partnership to Engage Marginalized Students in Antibiotic Discovery from Bacteria in Their Own Neighborhoods  

This talk will detail a collaboration between scientists at University of Illinois Chicago and middle school students of the James Jordan Boys & Girls Club in Chicago, who partner to perform a microbial antibiotic discovery pipeline together to explore bacteria collected directly from the students’ neighborhoods. 

IDBac: Using Mass Spectrometry and Bioinformatics to Create an Open-Access Database for Rapid Bacterial Identification  

Despite the proven effectiveness of MALDI-TOF mass spectrometry to rapidly identify pathogenic bacteria to the species/subspecies level in the clinic, researchers still have limited capacity to identify and dereplicate environmental isolates efficiently in the laboratory. To address this, Murphy and a multi-institutional team have collaborated to construct an open-access mass spectrometry (MS)-based bioinformatics pipeline, and accompanying bacterial database, to be available to researchers worldwide. The project details the digitization of protein MS profiles from part of the USDA NRRL bacterial library, a collection from NASA’s Jet Propulsion Laboratory, a human microbiome collection from University of Illinois Chicago and several collections from academic labs. Data are visualized in an open-access, semi-automated pipeline, IDBac, that was developed in the Murphy lab. Researchers can use the IDBac MS protein fingerprint database to identify unknown isolates, group and compare hundreds of unknown isolates based on phylogenetic similarity, compare groups of isolates based on user-uploaded metadata and compare differences in specialized metabolite production between phylogenetically similar isolates. 

Grant Writing Workshop for Young Scientists  

Murphy is well qualified to advise young scientists in grant writing. He developed and teaches a course at University of Illinois Chicago, titled “Science Writing and Storytelling,” and has served as a panel member on several grant writing-themed events for the NIH. A 1- to 3-hour interactive grant writing and storytelling workshop is proposed for pre- and postdoctoral students at ASM-sponsored meetings. 

Career as an Academic Professor Workshop  

Murphy has served as a panelist for career development on several occasions. A 1-hour interactive presentation will be implemented, detailing the “hidden curriculum” behind being an academic professor (i.e., the aspects of a professorship that are often not communicated to trainees interested in academia). These include how to spend a startup package, how to write and submit grant applications, how and when to serve on committees, how to plan your research around your tenure clock, how to decide when to submit a grant, etc. This is designed for pre- and postdoctoral students at ASM-sponsored meetings. 

In addition to providing lectures for branch meetings, ASMDL lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Judge posters and/or oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.

Dissecting Microbe-Host Interactions in the Mammalian Gut Using Systems Genetics Approaches

Defining the general principles that govern microbe-host interactions in the gut ecosystem is a daunting task. Over the last decade several studies have shown that host genetics influences intestinal microbiome composition, and genetic loci modulating abundance of bacterial taxa and metabolism have been discovered. A central premise of these approaches is that genetic variation drives phenotypic differences. This powerful premise produces an anchor for creating robust causal network models that can connect microbes, metabolites and host genes to complex phenotypes. Thus, when traits without known relation (e.g., abundance of a microbe and a particular metabolite) are highly correlated at a specific host locus, novel hypotheses emerge connecting these traits. Follow-up hypothesis-driven studies can then be conducted to test these novel ideas. During my talk I will introduce commonly used systems genetic approaches and discuss examples of how we have applied these methods to identify novel molecular players that potentially shape microbe-host interactions in the mammalian gut.

Exploring the Consequences of Interpersonal Variation in Gut Microbial Metabolism of Dietary Fiber

Consumption of diets rich in fiber and polyphenols (e.g., whole grains) has been associated with protective effects against metabolic and cardiovascular disease. However, clinical intervention studies have revealed a large degree of interpersonal variation in the effects associated with consumption of diets rich in fiber and polyphenols, with a subset of individuals not exhibiting any benefits. During my talk I will discuss examples of how bacterial metabolism modifies specific nutrients and how differences in gut microbiome composition can contribute to interpersonal variation in the host responses to dietary fiber.

Gut Bacterial Metabolism and Cardiometabolic Disease

Association and experimental studies have implicated gut microbiota in a number of risk factors for atherosclerosis, including insulin resistance, altered bile acid metabolism, inflammation and obesity. A major mechanism by which gut bacteria contribute to atherosclerosis and other diseases is via the production of metabolites that enter host circulation. During this talk I will discuss key microbially-derived metabolites that influence metabolic and cardiovascular disease, the bacterial pathways involved in their production and what is known about how these metabolites influence disease.

Workshop on Gnotobiotics

Studies establishing causal links between gut microbes and disease often use germ-free mice, which enable precise manipulation of colonizing microbes. While they have only been widely used in the last 2 decades, the first germ-free animals were generated >100 years ago. In this workshop I will discuss how germ-free mice are generated, maintained and monitored, and provide a short review of the fascinating history of gnotobiotics.

In addition to providing lectures for branch meetings, ASMDL lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Judge posters and/or oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.

Fungi and Interferons Meet at Unexpected Places  

This lecture focuses on understanding mechanisms of immune-mediated control of fungal infections in the lung and the role of interferons (IFNs), describing the multifaceted role of these cytokines in antifungal defenses and how they regulate host responses to microbes. In this context, I will discuss our novel finding that type I and III IFNs are necessary for defense against invasive aspergillosis. We uncovered that monocytes are an essential source of type I IFN, which is required for optimal expression of type III IFN. We determine that type III IFN is essential for the activation of antifungal neutrophils. We employed a combination of gain-of-function, loss-of-function and mouse models with cell-specific gene defects to support our conclusions. 

Unexpected Effects of a Fungus-Based Vaccine Candidate  

Fungal pathogens typically affect individuals with some defects in their immune response, but on the other hand, they are armed with multiple mechanisms that interfere with host defenses and promote immune evasion. Thus, the generation of antifungal vaccines is a challenging task. In this lecture, I will discuss our work with a vaccine strain of Cryptococcus neoformans. This Cryptococcus-based vaccine confers potent protection against homologous infection, but intriguingly, it also protects against other invasive mycoses. I will discuss our studies aimed at defining the mechanisms of vaccine-induced protection against fungal pathogens. 

In addition to providing lectures for branch meetings, ASMDL lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL lecturer has indicated interest in doing the following:

• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.

Prevention of Healthcare-Associated Infections (HAI)  

Healthcare-associated infections remain a major challenge for prevention and control, especially Clostridioides difficile infection (CDI). This topic will cover ways to effectively prevent and treat CDI and related HAIs, including the role of fecal microbiota transplantation and related therapeutics. 

Systems Engineering Approaches to Prevent HAIs  

Healthcare organizations are complex interconnected systems. Prevention of HAIs requires behavioral change on the part of the healthcare worker. A systems approach is useful in optimizing the system to help the work of the human. This novel approach to HAI prevention is generalizable to other communicable diseases. This lecture will review and discuss the use of these methods and their impact on HAIs. 
  

Challenges in Antimicrobial Stewardship in Immunocompromised Hosts  

Immunocompromised hosts are prone to infections, especially by drug-resistant bacteria. Effective antibiotic stewardship is essential, yet challenging, in this population. This lecture will review potential strategies to implement effective antibiotic stewardship in immunocompromised patients. 

In addition to providing lectures for branch meetings, ASMDL Lecturers are available to participate in career development and mentoring activities for trainees at Branch meetings. This ASMDL Lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.

Global Impact of Emerging Infections

There are multiple factors responsible for causing recent emerging infectious diseases. Today's enormous movement of humans, animals and materials provides an arena of mixing diverse genetic pools at an extremely rapid pace. Microbes have been evolving with an even faster speed, which has constantly posed a major threat to global health. How to increase the awareness of these emerging infections has become an important issue in modern practice of medicine, public health and laboratory diagnosis. 

Solving the Puzzle of Unexplained Outbreaks with a Multidisciplinary Approach

Many emerging pathogens were discovered during unexplained outbreak investigations. The intertwining complexity of emerging pathogens with their diverse tissue tropisms, direct effects on host cells and multiphasic immunological responses, is beyond the expertise of a single discipline in modern medicine. The diagnosis, treatment and prevention of these emerging infections need a multidisciplinary approach. Laboratory methods are essential to identify an etiologic agent from testing clinical samples. These methods, including traditional microbiological techniques, conventional immunological assays and modern molecular methods, remain the mainstay in today’s practice of clinical microbiology and infectious disease medicine. Pathology plays a key role as a bridging subspecialty in such a multidisciplinary approach. Pathologic examination can establish a more specific diagnosis correlated with clinical manifestations. Recent advances in molecular biology have revolutionized the practice of pathology and laboratory medicine.

One Health and Recent Challenges of Emerging Zoonoses

“One Health” is an approach that recognizes the interconnections between people, animals, plants and their shared environment to achieve optimal health and well-being outcomes. It needs a cohesive collaboration among multi-disciplinary expertise at local, regional, national and global levels. An important area in One Health approach is the control of zoonoses or zoonotic infectious diseases. Zoonoses are a complex group of diseases caused by a remarkable diversity of pathogenic microorganisms that ordinarily reside in animals. Approximately 75% of recent emerging infections are zoonoses. These diseases have caused severe illness in humans and posed major threats to global health. Improving diagnostic capability, increasing awareness and enhancing surveillance are all crucial measures to help deal with these emerging challenges of zoonoses.

Diagnosis of Infectious Diseases with Modern Technology

Diagnosis of infectious diseases needs a combined evaluation of the patient’s history, clinical manifestations and physical examination, but it is often insufficient to determine the specific infectious etiology. Laboratory methods are essential for identifying an etiologic agent from testing clinical samples, such as blood, serum, nasopharyngeal swab, etc. These methods, including traditional microbiological techniques, conventional immunological assays and modern molecular methods, remain the mainstay in today’s practice of clinical microbiology and infectious disease medicine. Nevertheless, there are technical and logistic issues associated with these methods, and the test results often lack a clinic-pathologic-microbiologic correlation that can confound the interpretation of their clinical significance. Pathologic examination, if available, can establish a more specific diagnosis correlated with clinical manifestations. The practice of modern pathology has evolved from using morphologic pattern recognition as the main tool to a sophisticated medical subspecialty by applying a wide array of advanced immunologic and molecular techniques on top of the traditional methods.

In addition to providing lectures for branch meetings, ASMDL Lecturers are available to participate in career development and mentoring activities for trainees at Branch meetings. This ASMDL Lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Judge poster and/or oral presentations.
• Give a separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.

It’s Complicated: The Global Problem of Harmful Cyanobacterial Blooms  

Blooms of toxin-producing cyanobacteria are on the rise around the globe. Yet it is only recently that researchers have begun to disentangle the many reasons. Using state-of-the-art molecular ecology, the lecture will dig into how big data (RNA sequencing, metabolomics) is being used to show how nutrients, viruses and climate change are intertwined in driving the proliferation of toxic cyanobacteria. With a focus on Lake Erie, this work also contains insights from fresh waters around the world. 

Small Stories about Giant Viruses  

Giant viruses contain genes and drive functions that rival “cellular life.” The lecture will provide insight into how viruses shape ecosystem function, with a focus on giant viruses in the Nucleocytoviricota. As a case study, the Aureococcus anophagefferens virus (now known as Kratosvirus quantuckense) that infects the causative organism of the brown tides along the U.S. Eastern Seaboard is but one such model. Drawing from 20 years of DNA and RNA sequencing, as well as the deployment of state-of-the-art new techniques, e.g., cryo-transmission electron microscopy (TEM), the presentation provides insight on genomic expansion and the potential for virus particles to carry functional genes and proteins, giving them metabolism independent of their hosts. 

Molecular Biology on the High Seas  

The tools of molecular biology are changing how oceanographers look at the world and how biological processes (and who undertakes them) occur. Drawing on deep transcriptional sequencing from research completed in the Southern Ocean as well as in the heart of the Bermuda Triangle, the lecture asks not only what microbes do in the ocean but also how and why—and in the process, provides new insight on oceanic biogeochemistry and the potential state of the ocean in future climate scenarios.

In addition to providing lectures for branch meetings, ASMDL Lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL Lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.

Toxins, Toxins, Everywhere: Turning Foe into Friend  

This presentation provides an overview of the prevalence, modes of action and potential applications of toxins. Toxin-like modules are being identified in an ever-growing number of bacterial genomes. Bacterial toxins have played a myriad of fundamental roles in basic and clinical microbiology, from their first discovery as causes of disease to their implementation as tools for understanding cell biology, to their beneficial therapeutic applications as immunomodulators, anti-cancer treatments, treatments for neuronal disorders, biologic cargo-delivery platforms and many still untapped potential applications.

Clinical Applications of Bacterial Toxins: Mechanism of Action and Therapeutic Uses of Botulinum Neurotoxin

This presentation provides an overview of how bacterial protein toxins act on cells and can be used as target-cell-specific therapeutic agents. Botulinum neurotoxin is given specifically as an example. Attendees gain an understanding of how botulinum neurotoxin disrupts neurotransmission and is used as a therapeutic. Attendees gain an appreciation of the potential consequences of misuse of botulinum neurotoxins in cosmetic and non-cosmetic applications, gain an appreciation of their potential therapeutic application as augmenting agents during wound healing to prevent severe scarring and to treat keloids and learn about the development of bacterial toxin-inspired drug delivery (BTIDD) platforms. (This presentation has been used for CME credit by the OSF Healthcare System.) 

Global Biosecurity and the Antibiotic Resistance Crisis  

This presentation brings to light the ongoing and escalating antibiotic resistance crisis. The talk outlines the diminishing antibiotic pipeline and the emergence and spread of antibiotic resistance, with emphasis on the problem being of critical concern for everyone. Attendees will gain an understanding of how antibiotic resistance arises and spreads and gain an appreciation of the many factors that have led to the current crisis situation. Attendees will gain an appreciation for the challenges associated with bringing newly discovered compounds with antibiotic activity through the development, testing and regulatory approval processes, and finally, to market. Attendees will also gain insights into the perspectives of different stakeholders and some promising measures that are underway that might help tackle the problem. (This presentation has been used for community outreach).  

Food Safety: The Case for Food Irradiation—Ensuring 100% Germfree  

This presentation provides insights about the use of food irradiation and its application toward ensuring food safety. Attendees will learn about the factors that led to our current concerns about food safety and why this is a growing problem. Attendees will gain an understanding of what food irradiation is and how food irradiation might help mitigate food contamination, thereby providing a possible solution to improve food safety. (This presentation has been used for community outreach.) 

GMOs and Food Insecurity: Problem or Solution?  

This presentation discusses GMOs and provides an overview of the issues surrounding their perceived risks and benefits. Attendees will learn about what GMOs are and the pros and cons of using GMOs, including perspectives from different stakeholders. Attendees will also gain an understanding of how GMOs might serve as a possible solution for the impending global food insecurity problem, including protection against food spoilage and crop damage and enhancing nutritional value of food. (This presentation has been used for community outreach.) 

In addition to providing lectures for branch meetings, ASMDL Lecturers are available to participate in career development and mentoring activities for trainees at branch meetings. This ASMDL Lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Judge posters and/or oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.
• Other: Give talks/lead discussions on topics such as 
  • Navigating the Tenure-Promotion Process: Strategies for Balancing Research, Teaching, and Service. 
  • Balancing a Career in Science and Family. 
  • Why So Few? Women in Science, Technology, Engineering and Mathematics. 
  • The Gender Wage Gap: Pay Equity is Still an Issue that Impacts Everyone.
  • Active-Learning and Scientific Teaching—Strategies for Enhancing Student Engagement at Scale.
  • Navigating Tricky Situations. 
  • Taking the Wheel: How to Navigate Difficult Conversations.

HCMV Pathogenesis—The Use of Monocytes as Trojan Horses for Viral Dissemination  

Human cytomegalovirus (HCMV) pathogenesis is caused by widespread dissemination of the virus throughout the infected host. HCMV is a myelotropic virus that manipulates and takes control of monocytes to favor hematogenous dissemination. Our studies show that HCMV utilizes monocytes as Trojan horses to promote movement from blood to organ tissue, allowing for life-long persistence and virus-associated organ disease. ‘Omics, flow cytometry and molecular profiling have identified some of the critical features of these infected immune cells. 

Why Understanding Host-Pathogen Interactions is Needed to Design Better Mitigation Strategies; HCMV Infection as a Model  

We have established a viral infection model using clinical isolates of HCMV to infect the relevant in vivo targets of peripheral blood monocytes and bone marrow progenitor cells. Thus, we have established a relevant infection model to better understand the process of persistence, latency and reactivation. Using this model, we are deciphering and identifying the molecular drivers of infection and latency to provide new potential therapeutic targets to mitigate viral disease. 

Unique Viral Entry Pathways Are Seen in Monocytes Following Human Cytomegalovirus Infection and Entry

HCMV infection is critical for in vivo infection, long term viral persistence and virus-associated pathogenesis. Infection of these critical immune cells is distinct from infection of other cell types. Through molecular and cellular experimentation, we have identified what appear to be novel pathways that the virus utilizes to infect these cells, which in turn promote the long-term persistence and disease observed in the infected host. Specifically, we have utilized a combination of high-resolution microscopy and molecular and biochemical analyses to identify key intracellular trafficking pathways involved in viral entry. 

How Receptor-Ligand Signaling Following HCMV Infection Promotes Persistence and Disease Following HCMV Infection  

HCMV promotes robust cellular activation following infection. Select viral attachment glycoproteins serve as critical regulators of the outside-in signaling that occurs following viral attachment. HCMV targets blood monocytes and organ macrophages for persistence, and ultimately, because that infection of these cell types is the root cause of disease, we have focused our studies on understanding virus-mediated receptor-ligand signaling following infection of these critical immune cells. Studies using ‘omics and molecular profiling have identified the distinct signaling events and key drivers of infection that appear critical for infection of monocytes. 

In addition to providing lectures for branch meetings, ASMDL Lecturers are available to participate in career development and mentoring activities for trainees at Branch meetings. This ASMDL Lecturer has indicated interest in doing the following:

• Attend poster sessions and oral presentations.
• Judge posters and/or oral presentations.
• Give separate lecture for students.
• Participate in informal gatherings/discussions—at dinner, reception, etc.
• Attend an ASM Student Chapter meeting.
• Participate in a career forum.
• Hold a “Meet the Speaker” session.