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Dr. Hallam teaches MICB 425 Microbial Genetics in Winter semester, Term 2.

Note: This course will be available in 2012. It is intended to be a companion to MICB 325 Microbial Genetics. The following is a tentative course description.

MICB 425 Microbial Ecological Genomics

Topical outlines for a series of lectures comprising specific "content modules" follow the course description. Specific learning outcomes are inserted into each topic outline in bulleted form. These learning outcomes are intended to form the basis for PRS i.e. "clicker" focus questions guiding in-class discussion, problem sets, homework assignments and examinations. Each is written to indicate what a student should be able to do after the lectures.

Course Description

This course explores the intrinsic and extrinsic forces driving genome evolution within the bacterial and archaeal domains of life. Content areas include barriers and gateways to horizontal gene transfer, microbial species concepts and community genome structure, function and dynamics, and the ecological impacts of microbial genome diversity. Drawing on primary scientific literature, the course emphasizes a problem solving approach using current experimental methods and design such as high throughput sequencing and screening methods, discovery and application of plasmids, phage and other mobile genetic elements.

Rationale and Intended Users

It is now recognized that the vast majority of biodiversity on the planet is represented by microbial life. Although this diversity operates at a scale below the resolution of our senses, it shapes Earth systems at a fundamental level. It is important to understand the genetic basis for microbial biodiversity, how it arose and continues to evolve. To do this, one must also understand the experimental logic, explanatory power, and the limitations of methods and approaches used in the study of microbial biodiversity. This course is intended for any student with sufficient genetic and biochemical background interested in understanding the nature, extent and importance of Earth’s unseen majority.

Overall Learning Outcomes

By the end of the course, students will be able to
  • Evaluate different methods for studying the taxonomic and functional diversity of naturally occurring microbial communities and cultured reference strains.
  • Explain interconnections between microdiversity, genomic diversity and metabolic potential and their relationship to microbial species concepts.
  • Comment on the ecological role or impact of microbes and microbial diversity as they relate to individuals, populations of microbes and multicellular organisms, Earth systems and the biosphere.
  • Develop genetic screens combining classical and modern methods.
  • Develop experimental workflows to identify the biological properties of genes, biochemical pathways or communities under laboratory or environment conditions.
  • Discuss the roles of mobile elements in the generation of genomic diversity, microbial adaptation and response, and the development of new tools for gene discovery and genetic engineering.

Lectures 01-02 "Logistics"

  1. Syllabus
  2. Survey
  3. Pretest
  4. Movie = Powers of Ten (a movie about scaling relationships in nature)

Lectures 03-05 "Genomic Integrity & Adaptive Mutation"

  1. On the origin of mutants
  2. recA and DNA repair pathways
  3. The SOS regulon and hypermutable states
  4. H. pylori evolution and phenotypic diversification
  • Compare and contrast DNA repair pathways and modes of regulation
  • Describe the SOS regulon based on the outcome of genetic screens
  • Explain the role of DNA polymerase IV in adaptive mutation
  • Evaluate H. pylori diversity in the context of human-microbe mutualism and disease
  • Discuss the role of phase variation in metabolic adaptation and host response

Lectures 06-08 "Controlled Evolution Studies"

  1. The dynamics and genetic bases of adaptation
  2. Tradeoffs and the specificity of adaptation
  3. Emergence and consequence of mutator phenotypes
  4. Drift and decay in very small populations
  • Interpret studies of microbial evolution in chemostat and serial transfer systems
  • Compare and contrast fitness trade-offs associated with resource specialization
  • Explain how selection under starvation conditions promotes mutations
  • Describe the use of microarrays to identify convergent adaptive mutations
  • Discuss phenotypic divergence and parallel evolution within replicate populations

Lectures 10-12 "Modes of Horizontal Gene Transfer (HGT)"

  1. Agents of open source evolution
  2. Competence and natural transformation
  3. Bacterial conjugation machines
  4. Transduction systems
  • Compare and contrast competence regulatory networks in Gram-/Gram+ bacteria
  • Evaluate gene expression studies of competence and transformation systems
  • Describe a model for polarized DNA uptake and recombination
  • Interpret experimental evidence on the role of plasmids in biofilm formation
  • Comment on the role of phage in HGT and genome evolution

Lectures 13-15 "Mobile Gene Cassettes"

  1. Transposon form, function and regulation
  2. Bacteriophage mu: a jumping gene machine
  3. Integron shuffling and strain level diversification
  • Describe the structural, functional and regulatory properties of IS and Tn elements
  • Comment on the relationships between conjugative plasmids and transposons
  • Discuss the genomic features and life cycle of phage mu
  • Outline experimental methods to study integron mediated cassette reshuffling
  • Describe a model for gene flow between mobile genetic elements and genomes

Lectures 16-18 "Genomic Islands in Pathogenic & Environmental Microbes"

  1. Discovering the pks Island
  2. Cyclomodulins and cell cycles
  3. The ecology of conflict
  4. Genomic islands in the sea
  • Outline experiments examining effects of E. coli pathogenicity islands on host cells
  • Explain how a virulence determinant can be both a toxin and a survival factor
  • Discuss how metabolic islands promote niche adaptation and genome divergence
  • Differentiate between genomic backbone and island features
  • Discuss the role of phage in generating genomic diversity within island regions

Lectures 19-21 "Barriers & Gateways to HGT"

  1. The HGT continuum
  2. H-NS and Xenogenic Silencing
  3. CRISPR-mediated cellular immunity
  • Outline a five-step model for horizontal gene transfer
  • Compare and contrast genetic mechanisms that promote or hinder HGT
  • Discuss the role of H-NS in xenogenic silencing and stealth functions
  • Describe the basis for CRISPR-mediated immunity to mobile genetic elements
  • Evaluate experimental methods to detect HGT

Lectures 22-26 "The Role of Ecological Theory in Microbial Ecology"

  1. Microbial species definitions in a postgenomic era
  2. Open and closed genotypic systems
  3. Measuring diversity and species richness
  4. Migration and endemism in bacterial populations
  • Discuss a role for comparative genomics in formulating microbial species concepts
  • Develop experimental workflows to study naturally occurring units of diversity
  • Evaluate the ecological significance and environmental dynamics of these units
  • Differentiate between microdiversity, genomic diversity and metabolic potential
  • Comment on forces mediating divergence and cohesion in microbial populations

Lectures 27-30 "The Meaning of Microbial Diversity"

  1. The unseen majority
  2. Enrichment cultures from nature
  3. Environmental Koch’s postulates
  4. Linking field processes to agents
  • Comment on the ecological significance of microbial diversity
  • Design and interpret workflows for the study of indigenous microbial communities
  • Discuss the application of Koch’s postulates to the study of microbial communities.
  • Evaluate methodological approaches for measuring in situ physiological processes

Lectures 31-36 "Through the Looking Glass of Environmental Genomics"

  1. Inferring the metabolic potential of indigenous microbial communities
  2. Case studies: acid mines, ocean surveys, methane mysteries, expanding oxygen minima
  3. Life and the evolution of the biosphere
  • Describe methods of environmental genomic library construction and screening
  • Outline the power and limitations of environmental genomic analysis
  • Discriminate between phylogenetic and functional gene anchors
  • Evaluate statistical methods for composite assembly and pathway reconstruction
  • Discuss the impact of microbial community metabolism on biosphere evolution

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