2017 Course Description


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Application deadline is March 12, 2017.

 

 

Course Directors: 

Richard Neher (Biozentrum, Basel), Paul Rainey (ESPCI, Paris), Boris Shraiman (KITP, UCSB)
 

Course Instructors:

R. Dutton (UCSD), D. Huson (U. Tübingen), T. Julou (Biozentrum, Basel), H. McCann (NZIAS), Richard Neher (Biozentrum, Basel), J. Quick (U. Birmingham), Paul Rainey (ESPCI, Paris), Boris Shraiman (KITP, UCSB), E. Toprak (UT Southwestern), E. Wilbanks (UCSB)


Guest Lecturers (partial list):

J. Bergelson (U. Chicago), O. Cordero (MIT), S. Copley (U. Colorado), S. De Monte (ENS, Paris), M. Desai (Harvard), M. Doebeli (UBC), I. Gordo (Gulbenkian Inst.), O. Hallatscheck (UC Berkeley), T. Hwa (UCSD), D. S. Fisher (Stanford), E. Koonin (NCBI), R. Lenski (MSU), B. Levin (Emory), A. Murray (Harvard/HHMI), F. Rohwer (SDSU), A. Spormann (Stanford), G. Suel (UCSD/HHMI), P. Turner (Yale), J. Weitz (Georgia Tech), N. Wingreen (Princeton)
 

Course subject

Microbial communities play a profoundly important role on all scales, from carbon cycling in the ocean to cellulose utilisation in the gut of a termite. Microbial communities provide the foundation for ecosystems on the planet and are increasingly recognized as a major factor in human health. While it is convenient to study separate microbial species as they interact with the environment, in reality the  environment experienced by any one microbe is shaped by its interaction with other members of the local ecological community. Behavior of an individual cell is intertwined with the behavior of other community members and many of the metabolic functions of a cell can be  “outsourced”, making the community the relevant physiological unit. Understanding the function of microbial communities is the current frontier of science at the interface of microbiology with ecology and evolution. What are the “forces” that bind these microbial communities? Is the community more than the sum of its parts? What are the “parts” and how do they interact? How do microbial communities respond and adapt to environmental challenges and how do they evolve? What is the role of horizontal gene transfer? What is the role of competition within a community and how is the diversity maintained?  

The course will introduce students to the fundamental questions and to the promising approaches towards the study of microbial communities. Students will get a hands-on introduction to microbial communities in the lab and will gain experience with new technologies for studying microbes. Students will be working in the groups of 4-5 (under the guidance of instructors and TAs) on different projects which will involve microbiology lab work, sequencing, bioinformatic analysis and modeling. Within the framework of the group projects  students will have an opportunity to define and pursue their own research questions. A number of short lecture series will introduce basic concepts and new developments. We expect that, even under the constraint of a 4 week course, students will be able to generate interesting “preliminary data” and perhaps make a discovery or two.

The course will run side by side with the KITP workshop Eco-Evolutionary Dynamics in Nature and the Lab. Students will attend the lectures and seminars and will have the opportunity to interact with numerous senior researchers that will be participating in the workshop.

 


Mini-Courses

  • Daniel Huson: Metagenomic sequence analysis (2 lectures + 3h “practical”)
  • Eugene Koonin and Richard Neher: Bioinformatics of microbial pan-genome (2 lectures + 3h “practical”)
  • Joshua Quick: Nanopore sequencing bootcamp
  • Alfred Spormann: Introduction to cellular and community metabolism (3 lectures)
  • Joshua Weitz and Forest Rohwer: Quantitative viral ecology (3 lectures)
  • Michael Doebeli and Daniel Fisher: Introduction into mathematical modeling of ecological and evolutionary dynamics (2 lectures+3h tutorial)

 


 

EXPERIMENTAL PROJECTS (preliminary list)

 

Rachel Dutton: Microbial communities on cheese

The microbial communities of cheese are relatively simple, easily culturable, rich in species interactions, and undergo reproducible dynamics of community assembly. They are hence ideal systems to study general properties of microbial communities. During the course, we will:

  • analyse time series sequence data of community dynamics
  • isolate species and sequence and assemble their genomes using NanoPore technology
  • study horizontal transfer within cheese communities.


Thomas Julou: Single cell phenotyping to study phage-bacteria interactions

In a complex microbial community, phages, nutrients, toxins, and other parameters are unpredictable. Bacteria respond heterogeneously to changing environments and this heterogeneous response can only be studied at the single cell level.  Using a “mother-machine” we will explore single cell responses to fluctuations in nutrients and phage. We will:

  • Use the mother machine to study the responses of bacteria to fluctuating nutrients
  • Explore dynamics of the interaction between phages and bacteria
  • Determine phage life history parameters

Joshua Quick: Nanopore boot camp

Sequencing technology is currently undergoing a second revolution from short-read to long-read sequencing. Nanopore Technologies has developed hand-held sequencers, the MinIon, with very short turn-around times that we will use during the course to sequence. We will:

  • use nanopore long read sequencing to assemble genomes from cheese and marine communities
  • metagenomic and environmental sequencing
  • quantify rearrangements and phage integrations using long reads


Honour McCann: Phylogeography and pangenomics of a kiwifruit canker pandemic

In this project, we will isolate bacteria from California-grown kiwifruit leaves using droplet technology, sequence a sample of these genomes, and analyze several hundred genomes of the kiwifruit pathogen Pseudomonas syringae obtained during the course of a recent global pandemic.  By comparing genomes in context of place and time of sample acquisition it is be possible to understand the evolutionary origins of the pathogen, identify the core genome and infer the core genome phylogeny.  A particularly dynamic component of the genome is marked by integrative and conjugative elements (ICEs) whose evolutionary origins are challenging to discern (but worth it). We will:
  • Use millifluidic technology [see / link to below] to isolate bacteria from leaves and process for sequencing in a single step.
  • Engage with new computational approaches for inferring biogeography and evolutionary origins of microbes
  • Study the population biology of ICEs


Paul Rainey with Maxime Ardré, Guilhem Dulcier and Laurent Boitard: Millifluidics

Millifluidic technologies offer new opportunities for studying and manipulating 1000s of microbial populations / communities.  Cultures are maintained in 250 nl droplets of media separated by a plug of air and oil, all within a 0.5 mm teflon tube.  Data on microbial growth / metabolism / phenotype are gathered in real time and can be coupled to downstream tasks such as DNA sequencing or high-throughput phenotyping tools. We will:
  • Use MilliDrop technology to isolate leaf colonising bacteria
  • Explore population dynamics of siderophore producers / non-producers
  • Analyse interactions between community members
  • Perform statistical analysis on population data using custom-built pipelines.


Paul Rainey with Steven Quistad: Phage and the evolution of microbial communities

Lateral gene transfer mediated by phage, plasmids, integrative conjugative elements and similar genetic parasites stand to effect -- fuel even -- adaptation of communities of microbes.  Communities arising from a year-long experiment will be established at KITP.  The communities were established from independent 1 g samples of compost and have been allowed to adapt to growth on minimal medium with cellulose as the sole carbon in the presence or absence of lateral gene transfer (mediated by phage).  The effect of lateral gene transfer on community level function will be determined through empirical tests.  Individual community members will be identified and sequenced.  Additionally, terabytes of DNA sequence data from multiple time points / treatments will be available for analysis. We will:
  • Isolate and characterise by DNA sequencing community members (phage and bacteria).
  • Determine the effect of selection and lateral gene transfer on the evolution of communities via phenotypic assay.
  • Delve into the dirty depths of DNA data and discover promiscuous phage, malicious microbes and culturable obscurities.


Erdal Toprak: Building and running a morbidostat

A morbidostat is a versatile computer controlled continuous culture device that adjusts the growth environment to maintain a specified growth rate, for example by adjusting the antibiotic concentration in the medium. We will:

  • build a morbidostat device
  • morbidostat experiments to study evolution of antibiotic resistance
  • analyse time series data from morbidostat experiments by phenotyping and genotyping evolved populations


Lizzy Wilbanks: Pink berry microbial consortia

The pink berries are photosynthetic microbial aggregates composed primarily of two closely associated species sulfur-metabolizing bacteria.  These species carry out a tight-coupled, syntrophic sulfur cycle within these macroscopic aggregates that found at the sediment-water interface of intertidal pools in the Sippewissett salt marsh (Falmouth, MA).  During the course, we will:

  • compare different long-read data for analysis and assembly of metagenomes
  • analyze strain-level biogeography between aggregates and along spatial transect
  • investigate the phages associated with pink berries and immunity profiles of different isolates.