Santa Barbara Advanced School of Quantitative Biology Summer Research Course: Quantitative Microbiology across Scales

Course Directors: Ami S. Bhatt (Stanford) and Roberto Kolter (Harvard Medical School)

Course Subject

Bacterial populations are far from uniform collections of identical cells. Even genetically identical bacteria can differ strikingly in their behavior and function. Such cellular heterogeneity can have profound effects on the ecology and evolution of bacteria. Whether they are growing as individual cells or as members of microbial communities these heterogeneous populations respond to changing environments and in turn change their environments as a result of their activities. In this course, students will take quantitative approaches to analyze the dynamics of bacterial populations in different settings, from microfluidic devices to the surface of growing plants.

Specifically, the course develops experimental approaches to address these questions:

  • How do microbial populations spread and evolve with a living, growing host?
  • How do differences in metabolism and physiology determine where microbes grow, compete, and organize?
  • What determines when bacterial groups form, how they grow, and when they break apart?
  • What happens when different strains of a bacterial species get exposed to an unexpected environment, either alone or within a community?

Instructors: 

Glenn D'Souza (ASU), Mike McDonald (Monash University), Honour McCann (MPI for Biology), Paul Rainey (MPI-EB), Julia Schwartzman (USC), and Erik Van Nimwegen (Basel)

Lecturers (partial list):

The summer course is closely linked to the concurrent KITP program Microbial Heterogeneity: From Genetic Switches to Collective Behavior in Biofilms. Course participants will attend the program's daily research seminars as part of the course curriculum. Students and lecturers will also have frequent opportunities for less formal interactions. Sigal Ben Yehuda (Hebrew U.), David Berry (Vienna), Roby Bhattacharyya (Broad Inst.), Otto Cordero (MIT), Sujit Datta (Caltech), Diana Fusco (Cambridge), Zemer Gitai (Princeton), Ben Good (Stanford), Richard Neher (Biozentrum), Caitlin Pepperell (Wisconsin), Ophelia Venturelli (Duke), and Ned Wingreen (Princeton)

Course Structure

The course is 5 weeks, beginning with a one-week bootcamp, followed by 4-week experimental projects. Each group of 4-5 students works closely with an instructor and TAs, and projects will be designed to promote substantial cross-talk between groups. The daily routine involves two morning lectures and discussions, followed by lab work in the afternoons until late in the evenings. During the bootcamp, students will acquire skills needed to succeed in research projects. These include microbiology, microfluidics, high-throughput sequencing, quantitative analysis, and theoretical modeling. The morning lectures will take place in the context of the parallel running KITP program "Microbial Heterogeneity: From Genetic Switches to Collective Behavior in Biofilms", providing an excellent setting for discussion and exchange with program participants.

A typical day's schedule includes:

  • 2 morning talks at KITP
  • Lunch in a dining hall or campus cafe, with other course or program participants
  • Afternoon lab work
  • Dinner in a dining hall, followed by evening lab work and/or science discussions

On weekends, students can attend program BBQs and self-organize outings to the beach or around Santa Barbara.

Accommodations, Fees, and Financial Assistance

Students are housed in double-occupancy rooms in UCSB student apartments and provided with 19-meal plan at campus dining commons. The room and board fee is ~$3200. There are no other fees or tuition. Students who need financial assistance can request it in their course application form; financial need does not affect an applicant's chances of admission. A limited number of single rooms are available for a ~$1500 supplement.

Descriptions of Experimental Modules

Metabolism & physiology determine where bacteria grow, compete, and organize

Instructor: Glen D'Souza
TAs: Somok Banerjee and Le Pham

How do differences in metabolism and physiology determine where microbes grow, compete, and organize in space? In this module, students will use microfluidic experiments and quantitative imaging to investigate how microbial communities emerge from interactions between cells and their local chemical environment.

One project (connected to Mike McDonald's module) will examine how plant-associated exudate sugars structure microbial colonization. Students will work with communities composed of fluorescently labeled E. coli strains carrying defined metabolic knockouts and follow their growth in microfluidic growth chambers. By varying available sugars and combining strains with different metabolic capabilities, we will test how resource use, competition, and genotype shape spatial community organization.

A complementary project (connected to Julia Schwartzman's module) will focus on alginate-degrading marine bacteria like Vibrio splendidus. Here, students will ask how microbes modify their environment through metabolism and how those changes feed back to organize subsequent growth. Microfluidic imaging will be combined potentially with physiological reporters to visualize differences in cellular state and determine how metabolic heterogeneity, resource transformation, and environmental engineering generate spatial patterns within microbial populations.

Together, these projects will introduce students to a central theme in quantitative microbiology: how local differences in growth and metabolism scale up to the spatial organization of microbial communities.

Bacterial spread and evolution on a living, growing host

Instructor: Mike McDonald
TAs: Chris Blake and Storme De Scally

How do microbial populations spread and evolve with a living, growing host? How does the spatial structure of a root, with its changing nutrient profile and continually advancing tip, alter ecological and evolutionary processes? We will explore these questions using a gnotobiotic plant model, plating and culture techniques, DNA sequencing and microscopy.

The first project will ask whether colonization of the growing root tip is dominated by neutral genetic drift or behaves more like a travelling wave. Students will inoculate plants with two equally fit, fluorescently labelled bacterial strains, and measure how their relative frequencies change along the root using plating, microscopy and sequencing.

The second project will examine the dynamics and evolution of microbial communities growing on roots. Students will follow defined communities through root growth or repeated passage between plants, tracking changes in community composition and selected microbial traits. These communities could include microbes drawn from the other experimental projects.

Students will work collaboratively as part of one of these two broader project teams, designing and completing a tractable four-week experiment together. They will also interact with students across the other projects through the shared boot camp and collaborative sequencing and microscopy activities. In doing so, they will gain experience in culturing plant-associated microbes, quantitative experimental design, microscopy and DNA-sequence analysis.

Genomic Island Transfer Exploiting Jumbo Phages

Instructor: Paul Rainey

Can genomic islands (GIs) — pieces of bacterial DNA that cannot move on their own — exploit bacteriophages to achieve their own horizontal transfer? Building on  Zhao et al. (2025) (see also Penadés 2025), this project will investigate how such elements use jumbo phages to move through natural microbial communities. We will expose marked strains of Pseudomonas fluorescens SBW25 to filtrates from environments around Santa Barbara and ask whether locally occurring phages can transfer the kanamycin-marked genomic island I55 into a tetracycline-resistant recipient. If transfer occurs, we will sequence the resulting bacteria and hunt for the phages responsible. In a complementary experiment, we will introduce the known I55-mobilizing jumbo phage JPTI55 into environmental samples, recover cell-free filtrates, expose the filtrate to naïve SBW25, and sequence recipient colonies to ask whether the phage has captured and mobilized previously unknown genomic islands. Together, these exploratory experiments will probe the diversity, specificity, and ecological reach of phage-mediated gene transfer while giving participants experience in environmental microbiology, microbial genetics, phage isolation, and genome analysis. A related project for math-nerds (guided by Boris Shraiman) will develop models to explore the boundary conditions allowing persistence of GIs and the phages they exploit.

Determinants in the transitions between solitary and group living

Instructor: Julia Schwartzman
TA: Shloak Vatsal

Many bacteria alternate between solitary and group living, but what determines when groups form, how they grow, and when they break apart? Students will explore these questions using marine Vibrio strains that form physically associated groups while growing on alginate, a polysaccharide produced by brown algae. Quantitative light microscopy will be paired with mathematical models and targeted measurements of cellular physiology.

Group formation can occur when cells come together or remain together after division, and both routes are observed in our Vibrio models. The first project will bring together several students to measure group-formation dynamics as a function of cell–cell and cell–resource encounter rates. Students will vary the initial densities of bacterial cells and alginate resources and use existing physical models to estimate encounter rates. Each student will take ownership of a distinct experiment focused on a selected response, such as the probability or timing of group formation, growth rate, or group-size distribution. Some experiments may add a measurement of cellular physiology to test whether physiological state explains departures from the physical model. Together, these experiments will provide complementary views of how encounter dynamics shape group formation.

As bacterial groups grow, transport limitation can generate internal chemical gradients and physiological heterogeneity. Several students working within the second project will examine group integrity as a function of group size, growth, or physiological heterogeneity. Each student will focus on a defined relationship or apply a single perturbation to alginate degradation or a candidate adhesion mechanism. Some experiments may use a fluorescent reporter to relate a specific physiological state to group structure. Depending on feasibility, students may also analyze DNA methylation data or prepare selected samples for sequencing to ask whether population-level methylation patterns change during group development.

Students will work as part of one of these two broader project teams while completing their own tractable four-week experiment. They will gain experience culturing marine bacteria, designing and analyzing quantitative experiments using light microscopy. Depending on their individual experiment, they may also work with mathematical models, fluorescent reporters, or sequencing data.

Tracking heterogeneity and community interactions in experimental evolution

Instructor: Erik Van Nimwegen
TAs: Tamara Bojanic and Alberto Peruzzi

What happens when different strains of a bacterial species get exposed to an unexpected environment, either alone or within a community? Even within clonal populations, genetic heterogeneity is present at low frequency that selection can act on at very short time scales. In this course, students will combine experimental evolution with whole-population DNA sequencing, bioinformatics analysis, and mathematical modeling to understand how genetic heterogeneity drives short-term adaptation of different bacterial strains to new environments, and how cross-strain interactions affect the evolutionary dynamics when different conspecific strains grow together in a community versus by themselves.

Project 1: When different strains of bacterial species are inoculated in environments with non-standard nutrients or stresses, the resulting growth curves often exhibit substantial heterogeneity including long and highly variable lags, and even different rates of growth. Students will quantify lags and growth rates of different strains in such `challenging' conditions across multiple replicates, as a function of inoculum size, and as a function of passaging over multiple days. DNA sequencing will be performed on selected populations from different replicates and days to track how genetic heterogeneity drives adaptation in these populations, the spectrum of the mutants that emerge, and their relative frequencies. Students will then characterize the behavior of selected mutants across a range of other environments to understand how these mutations affect phenotypes beyond the condition in which they were selected.

Project 2: Students will assemble small synthetic communities of different natural isolates of the same bacterial species, and observe their short term ecological and evolutionary dynamics by passaging them for 3–5 days in different environments. Growth curves of the community will be measured each day to track how population growth rates, lag times, and yields change in time, while DNA sequencing of the population will be performed at selected time points. By mapping reads to the known genomes of the constituent strains, students will quantify changes in strain frequencies over time, track the emergence of mutations and activation of mobile genetic elements. Comparing community dynamics to the growth of each strain in isolation will validate the presence of ecological interactions and their dependency on relative strain frequencies.

Students may either work with strains from a collection of natural Escherichia coli isolates, for which our lab has already obtained extensive genotypic and phenotypic data, or work with conspecific strains of another species of their interest, for example one studied in their own lab, or that is being investigated in another project in the course.