Santa Barbara Advanced School of Quantitative Biology


Application deadline March 24: Rolling review begins March 17

 


Course Subject:

Mobile genetic elements (MEs) can mediate rapid adaptation by introducing genes that encode novel functions related to pathogenesis, symbiosis and metabolism into host cells. MEs, and the accessory genes they carry, are as varied as the hosts and niches they are found within. Fuller understanding of the dynamics, constraints and consequences of ME movement will require interdisciplinary research merging computational and experimental approaches. This hands-on course will integrate laboratory experiment with quantitative bioinformatic analysis, providing students from diverse disciplinary backgrounds with new experience and skills that will assist them in developing rigorous, quantitative research in microbial evolution and ecology.


Course Faculty: 

Joanne Emerson (UC Davis), Benjamin Good* (Stanford U.), Roberto Kolter (Harvard Medical School), Honour Mc Cann* (MPI-EB), Richard Neher (U. Basel ), Boris Shraiman (KITP/UCSB), and Paul Turner (Yale U.) 
 
*Course Director

Guest Lecturers (partial list):

The summer course is closely linked to the concurrent KITP program Horizontal Gene Transfer and Mobile Elements in Microbial Ecology and Evolution​. 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. Confirmed program participants include Aude Bernheim (Pasteur Inst.), Devaki Bhaya (Carnegie Science/Stanford U.), Allison Carey (U. Utah), Ilana Brito (Cornell U.), Daniel Fisher (Stanford U.) Nandita Garud (Stanford U.), Graham Hatfull (U. Pittsburgh), Daniel Huson (U. Tübingen), Eugene Koonin (NCBI), Michael Laub (MIT), Katie Pollard (Gladstone Inst., UCSF), Martin Polz (U. Vienna), Paul Rainey (MPI-EB), Eduardo Rocha (Inst. Pasteur), Julia Salzman (Stanford U.), and Erik van Nimwegen (U. Basel).


Course Structure

The course is 5 weeks long, and runs concurrently with the KITP Program Horizontal Gene Transfer and Mobile Elements in Microbial Ecology and Evolution. Students will begin with a bootcamp on basic wetlab techniques, then break into project groups for the first section of wetlab projects. After wrapping up wetlab data collection and preparing samples for sequencing, students break for a drylab bootcamp. Students will then join and complete a drylab project. During this period, sequencing for wetlab projects will be completed. During the last week, students will analyse the data from their wetlab projects, and present their findings to the program.

The experimental projects are led by instructors and TAs working closely with groups of 4-5 students. Additional guest lectures and training modules will be provided throughout the course. Students regularly attend morning lectures offered as part of the KITP Program, then head off for lab work in the afternoon and evening. Students are welcome to join visiting lecturers and program participants for tea breaks and evening BBQs at the Munger Physics Residence. Weekends are open for students to explore and enjoy the many recreational opportunities in the Santa Barbara area.


Accommodations, Fees, and Financial Assistance

There is no tuition, lab fee, or room and board fee. Admitted students are provided with double-occupancy rooms in UCSB student apartments and a 19-meal plan at campus dining commons. A limited number of single rooms are available for a $2064 supplement. Students who need financial assistance with travel expenses can request it in the application form; financial need does not affect an applicant's chances of admission.


Experimental Projects

 Evolution of bacterial genomic structure (Richard Neher and Marco Molari)

Bacteria exchange genetic material horizontally, duplicate DNA, delete parts or invert stretches of their genome resulting in complex patterns of genetic diversity. Despite the overall diversity and structural complexity, the order of essential genes in bacterial genomes tends to be highly conserved and most of the horizontally acquired diversity is concentrated in hot-spots. In this project, we will construct genome graphs  of groups of recently diverged bacteria (specific sequence types) using PanGraph. PanGraph is a tool to detect shared homologous sequences between a large number of genomes and summarize it in a concise graph structure. Using this graph, we will quantify the rates at which horizontal processes add or exchange genes and will detect aforementioned hot-spots and characterize their sequence repertoire.

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Examining G x G x E interactions in evolution of bacterial-pathogen resistance to therapeutic phages (Paul Turner)

This project examines three lytic phages of Pseudomonas aeruginosa (PsA) that have been used successfully in FDA-approved emergency therapy to treat antibiotic-resistant pulmonary infections in humans. Each phage infects PsA using a different cellular receptor, and can select for host bacteria to evolve phage-resistance that either reduces virulence or switches hosts to become antibiotic sensitive (i.e., phage induced trade-offs). In week 1, students will challenge the phages to infect a collection of PsA strains that are cultured in different environments, to test how the culture conditions impact the spectrum of isolated phage-resistant mutants. These ‘rescue’ mutants will then be submitted for whole-genome sequencing, to analyze the loci underlying evolved phage-resistance. Week 2 will involve analyses of the genomic results. In addition, students will conduct phenotypic (growth) assays on the mutant isolates using automated spectrophotometers (microplate readers) and R programs that infer quantifiable bacterial traits, to conduct rigorous genotype-phenotype analyses. The overall goal is to generate a large dataset of novel results that will inform phage-bacteria-environment (G x G x E) interactions, useful for future emergency patient treatment leveraging phage-induced trade-offs in this important bacterial pathogen system.

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Dynamics of ICE movement in bacterial populations (Elena Colombi and Honour Mc Cann)

Integrative and conjugative elements (ICEs) are large, self-transmissible mobile elements that mediate the movement of ecologically significant genes across even distantly related membes of the Pseudomonas syringae species complex. Excision, conjugal transfer from the donor, and site-specific integration into the recipient can occur within fifteen minutes in vitro. Newly acquired ICEs can replace or recombine with ICEs already present in recipient cells, generating novel chimeric elements. ICEs are known to vector genes with functions associated with antibiotic resistance, pathogenicity and symbiosis, bacteriocin synthesis and more. For this project, we will start by performing transfer and competition experiments to assess the host range and fitness contributions of ICEs in different recipient strains. We will then set up and sequence a serial passage experiment to quantify rates of ICE transfer in mixed populations. Students will explore whether ICE proliferation is linked to their contributions to host fitness, or is selfish in nature.

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Rates of Horizontal Gene Transfer and Transposition in Non-Growing Bacteria (Roberto Kolter and Benedek Facskó)

Comparative genomics led to the insight that horizontal gene transfer events are the prevalent mode of bacterial genome evolution. We know much about the modes of horizontal gene transfer, i.e., transformation, conjugation, transduction, etc. Most of the past studies that measured the rates of these processes utilized fast growing populations. Yet, we know that in natural settings, bacteria seldom encounter conditions propitious for fast growth. In this project, we will quantitate the rates of transduction in non-growing or very slow-growing bacterial populations. As a complement, we will also follow the dynamics of mobile genetic elements in non-growing cells. In addition, we'll explore the ecological implications of the little-explored phenomenon of abortive transduction

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Spatial patterns of soil viral communities (Joanne Emerson)

Students will investigate spatial structuring of soil viral communities to identify patterns and drivers of community composition. The project will begin with sampling soil and wetland environments in the area, then enriching for viral communities via filtration. Students will extract DNA from filtered and unfiltered samples, then sequence the viromes and metagenomes using MinION and Illumina platforms. Viral genomes will then be identified, and viral community composition will be compared to identify ecological differences along the sampled gradients. Finally, students will look for evidence of horizontal transfer by searching for integrated prophages in microbial genomes and 'host' genes in viromes. 

 

What is the KITP QBio Summer Research Course?

Understanding fundamental problems in biology requires both advanced experiments and the quantitative/theoretical approach traditionally taken by physics. The Santa Barbara Advanced School of Quantitative Biology “QBio” summer course trains early-career scientists to integrate these different approaches by having them do it all–they take part in novel, team-taught lab experiments led by renowned faculty; they integrate quantitative modeling and theory into their experimental design and data analysis; and they become part of an interdisciplinary community of biologists and physicists. The course aims to teach students to communicate and collaborate with people with different and complementary backgrounds: eliminating the scientific language barrier is a major goal of the course. Students leave the course with an expanded network of peers, senior program participants and course instructors. Ideally, students emerge from the course with much broader scientific horizons and confidence in their own ability to chart the path of their own research.

Who should apply?

The course is geared toward advanced graduate students and postdocs, whose rigorous disciplinary training and significant research experience has prepared them to absorb material through high-level seminars and a research environment. The high instructor-to-student ratio and team-based project format create a supportive environment, but the course is intensive and fast-paced. With only 5 weeks to work, students must be self-driven to get results. Since participants do much of their learning from teammates and through informal interactions with program participants, openness to others’ ideas (particularly those from different scientific and cultural backgrounds) is crucial, and the confidence to initiate conversations with senior scientists help successful students make the most of their time at KITP. Successful applicants typically show curiosity, a clear idea of how the course will impact their research program, a desire to do interdisciplinary work, and strong quantitative skills.

What do students say about the course?

"Participating in research projects outside my PhD work and interacting with other researchers revealed that - (a) I am broadly curious about biology, (b) I can ask questions and formulate testable hypothesis and (c) I enjoy science. When one of the instructors admired my efforts in his project and offered me a postdoc position, I realized that my abilities to do science were greater than my perception and decided to develop them further by continuing in research." - Sapna Chhabra (2019)

“I think one of the greatest values of this course has been the ability to interact with people from different fields and be able to learn the jargon that they use in one field and understand it at a deep enough level that we can then have conversations and build on that. Being able to interact with the physicists, theorists, and other experimentalists has helped broaden my knowledge base and also made me more comfortable, as a student, being able to talk across different fields and learn from people doing very different types of research, but all interested in and centered around different kinds of questions.” - Jess Kanwal (2018)

 

“For me, the project was very helpful for understanding the gap between the idealized data we theorize about and the data we actually have, and the project and tutorials left me much more versed in common computational techniques for bacterial genomics. The morning talks and the connections built over many hours with the other students in lab and over meals was also inspiring and makes me more likely to continue pursuing an academic career.” - Michael McLaren (2017)

“The KITP/QBio summer course is quite unique in the world and has been a true accelerator for my career. It first gave me a broad, comprehensive and timely overview on the field of morphogenesis, from both physics and biology points of view. This has been critical to nurture my own research project and to successfully apply to group leader positions. As a theoretician, the school allowed me to perform my first biological experiments ever. I realized that 1) I was actually not too bad in doing experiments, 2) I’d probably very much like doing my own ones one day. . . . The practicals in small groups, mixing biologists and physicists was a fantastic opportunity to learn from each others and to gain better teaching skills. This was a perfect mix of theory and experiments, and a perfect setting to make emerge original research ideas.” - Herve Turlier (2016)