Course Outline and Philosophy

Biology 524

Strategies of Host-Microbe Interactions

Spring Semester, 2008             M,W 2.00-3.15               Coker 119

 

Jeff Dangl

email: dangl@email.unc.edu

office hours by appointment, please email

 

Statement of Purpose: In this course, we will be exposed to the richness of strategies that microbes use to access the nutrients afforded by their hosts. We will discuss pathogens that cause disease and also more subtle forms of host-microbe interaction such as mutualism and symbiosis. We will cover topics that are areas of active research, and we will therefore rely on recent reviews and primary research papers, as well as more basic text readings. We will largely concentrate on bacterial and fungal systems. This course will be very challenging, and there will be a heavy reading load. I hope to instill in students an appreciation for the breadth of this topic and the excitement that exists in this area. We will by no means cover it all!

 

Expect to spend at least 3 hours reading for each lecture. But there are few other homework assignments.

 

Required Readings:

 

(1) Book Chapters from a text called Bacterial Pathogenesis by Salyers and Whitt, 2nd edition (American SM Press, 2002) (denoted SW on the syllabus; these chapters will be made available as electronic reserved reading as pdf files).

 

To view your paper reserve items, click:

 

http://webcat.lib.unc.edu/search/a?searchtype=r&searcharg=biol524&submit=Search

The stable link that you requested to your electronic reserve items is:


http://laconia.lib.unc.edu/eres/coursepage.aspx?cid=3093

 

You can also try the direct connection at:

 

http://eres.lib.unc.edu.libproxy.lib.unc.edu/eres/coursepage.aspx?cid=3093&page=docs

 

 

(2) a variety of Research Publications and News Stories are all available as pdf files on the course web site.

 

Course Web Site:         http://www.bio.unc.edu/Courses/2008Spring/Biol524/

 

Mode of presentation: This course is intended for highly motivated people and I want it to be largely discussion oriented. I want you to learn to talk and write about science, and be able to understand and present scientific results.

 

This REQUIRES that you do the reading BEFORE each class. I hope that the course will be discussion-style, question and answer driven. I will give short, introductory lectures and then we will turn to dissection of a research problem. I want you to ask questions, and answer each other’s questions. I will facilitate the discussion and try to give the “facts” for you to operate on. If things slow down, I will call on people to answer questions in class. The goal is to stimulate you to not only read the material, but to learn and practice oral scientific critique.

 

Class participation is a must. Please don’t be shy about joining the discussion. If you have a question, it is highly likely that someone else in the group has the same one. There is no such thing as a “stupid question”; just ask.

 

Exams and Grading: Your participation in discussions and attendance will count for 25% of your grade. It will be obvious to me if you are not prepared, and that will detract not only from your learning experience and fun, but also from your final grade. The will be a midterm exam, also counting for 25% of your grade. I will give you two hours for this exam, and you will be required to sign an honor pledge for it. The remainder of your grade will be determined by an oral presentation (25%) and a “research proposal” style term paper (25%). These three participatory items are each described below.

 

Student Presentations and “Research Proposal”: In a month or so, we will draw dates for the presentations. Your written research proposals are due on Tuesday May 6, 5pm. No exceptions! It should be emailed to me as a pdf file. This will require you to learn to embed figures tables and drawings into a Word document and then to “print it” as a pdf using Adobe Acrobat. Learning these computer skills is part of the course. Several examples of excellent Presentations and Research Proposals from past years will be posted on the course web site (see below).

 

For the Presentation and Research Proposal, each of you should choose either a topic covered in the course, or a very similar one. You will have some time to think about what you are interested in, but note from the syllabus that OUTLINES of no more than 2 pages double spaced are DUE by email to me on Friday, March 14. I will be happy to receive them earlier, and to discuss them with you. Do not be afraid to choose a topic that we will not cover until near the end of the semester. There are certain advantages to approaching these topics without being biased. The reading lists will be available, and I will be happy to discuss the topics informally before we cover them in class with those of you in this position.

 

Each Presentation will be a 15 minute presentation of your term paper using overheads and / or slides, followed by a 5 minute discussion period. Both your talk and the “research proposal” have the following goals:

 

(1) To educate your classmates and me as to the nature of the biological problem under study and (2) to convince them that your proposed experiments have merit, and (3) will add to the knowledge base in that field. In real terms, get the proposal funded! This requires clarity, homework, and some exuberance for the subject.

 

I think you will find this format useful, and it will encourage each of you to develop ideas, read independently and find strategies that allow you to communicate complex topics in simple language.

 

Both your talk (15-20 Powerpoint slides MAXIMUM) and the Research Proposal should be arranged as follows (numbers in parentheses refer to upper page limits, double spaced, for each section)

 

            1) summarize your overall goals (best done in “bullet” or “outline” form).                              (0.5)

            2) briefly summarize the current status of the research area covered by your proposal.             (3)

            3) state the Specific Aims of your proposal (one or two clearly stated aims are sufficient).

                        AND describe why your Specific Aims are important to this research area.             (2)

            4) Describe in simple terms a set of experiments to address your Specific Aims.

Discuss the possible outcomes of each experiment and how you would interpret them.            (5)

            5) list of full references, use the format of the journal CELL

 

This is the typical organization of all graduate and post-doctoral fellowship applications, as well as a normal grant proposal. Citation of references and any figures, graphs, tables, or schematic representations of experiments proposed and possible outcomes or interpretations DO NOT count in these page limits.

 

Tutorials: You will see from the schedule that we will take one class week off before these presentations begin. During this time, I will schedule meetings with each of you separately to “coach” you a bit and help with ideas as to how to effectively communicate your ideas to the class. Consider this a “dry run”. Note that if you are one of the “early presentations” it will probably be advantageous to you if we schedule this meeting before the “tutorial period”.

 

Texts and Reading Lists: As stated above, you will be expected to read quite a lot for this course. I have tried to arrange the topics, in each case, first with a general review followed by examination of one of two primary research papers. Those of you who do not have very much experience reading primary research papers will find it overwhelming in the beginning. Stick to it.

 

Some keys for success: Draw pictures of the experiments described in the text--a simple re-statement in your own pictorial terms is often worth the proverbial thousand words! So keep pencil and scrap paper handy while you read. Always keep in mind the goal of the experiments, which are hopefully clearly stated in the Abstract or Summary at the beginning of each paper. Understand each figure on its own as an experiment. Pay close attention to what the authors conclude from their results--Are the conclusions supported by the data? Have the authors performed the correct “control” experiments to show that their experimental conclusions are right?

 

Computer skills: You are responsible for learning how to use Adobe Acrobat reader (it is free), EndNote or another reference management program, and you will also need to know MS Word and one presentation/drawing program, usually Powerpoint or Canvas. You may want to bring your laptop to class to have the reading material at hand. Otherwise bring print-outs of the papers. Learning to handle scientific publications electronically is part of this course. If you do not know how, go to ATN help Desk and find out!

 

Model Presentations and Research Proposals from past years:

 

Paper 1

Paper 2

 

Paper 3

Talk 1

Talk 2

 

Talk 3

 

 


Syllabus

Biology 524

Strategies of Host-Microbe Interactions

Spring Semester, 2008             M,W 2.00-3.15               Coker 119

 

 

Lecture:

 

1 W Jan. 9        Class Introduction: Review of Bacterial Genetics

 

In this first, very short week, please review your Bio 50 (now Bio 202) text. If you sold it, go find one in the library. There are several on Reserve for Bio 50 (now Bio 202) and they all have a Bacterial Genetics chapter. Review of plasmids, gene transfer (conjugation, transformation, phage transduction) and mechanisms of Gene Regulation in prokaryotes.

 

Here’s the Powerpoint slide show for Lecture 1 and Lecture 2.

 

 

2 M Jan 14        Continuation of Lecture 1. Guest Lecturer, Emily Fisher.

 

 

3 W Jan 16        Infection mechanisms of bacterial pathogens and methods of analysis.

 

SW chapters 2 and 3 (or from the 1st edition, as posted here, chapters 3, 6).

 

                        Here’s the Powerpoint show for Lecture 3

 

In addition, go to: http://www.bio.davidson.edu/courses/genomics/chip/chip.html. Go through this animation CAREFULLY to understand DNA array experimental techniques.

 

M Jan 21          Martin Luther King Holiday

 

“True compassion is more than flinging a coin to a beggar; it understands that an edifice that produces beggars needs re-structuring." MLK

 

Instead of just going home for a long weekend and lounging around, get involved in your community.

Honor the man.

 

 

4 W Jan 23        Strategies for identification of virulence genes.

Here’s the Powerpoint show for Lecture 4

Heithoff, D. M., et al. (1997) Dissecting the biology of a pathogen infection Trends in Microbiol. 5, 509-513. (an excellent systems review).

 

Valdivia, R. H., and Falkow, S. (1997) Fluroescence-based isolation of bacterial genes within host cells. Science 277, 2001-2011.

 

5 M Jan 28        Comparative Genomics and Understanding Virulence in E. coli

 

                        SW chapters 28 and 29

 

Here’s the PowerPoint show for Lecture 5

 

Medini, D. et al. (2005) The microbial pan-genome. Current Opin. In Genet. and Develop. 15, 589-594.

 

Dobrint, U. et al. (2004) Genomic islands in pathogenic and environmental microorganisms. Nature Rev. Microbiol. 2, 414-424.

 

Brzuszkiewicz, E. et al. (2007) How to become a uropathogen: Comparative genomic analysis of extraintestinal pathogenic Escherichia coli strains. Proc. Natl. Acad. Sci.,USA 103, 12879-12884.

 

Extra reading, if interested:

 

Welch, R.A. et al. (2002) Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc. Natl. Acad. Sci., USA 99, 17020-107024.

 

 

6 W Jan 30        Commonalities in bacterial pathogenesis: Type III secretion systems and delivery of virulence factors.

 

                        Here’s the PowerPoint slide show for Lecture 6

 

He, S. Y. et al. (2004) Type III protein secretion in mammalian and plant pathogens. Biochem. Biophys. Acta 1694, 181-206.

 

(a long review—do not get bogged down with the gene names; focus on the principles)

 

He, S.-Y., et al. (2001) The Hrp pilus in Type III protein secretion in Pseudomonas syringae. Science 294, 2556-2558.

 

Anderson, D., et al (1999) Reciprocal secretion of proteins by the bacterial type III machines of plant and animal pathogens suggests universal recognition of mRNA targeting signals. Proc. Natl. Acad. Sci., USA 96, 12839-12843.

 

 

7 M Feb 4         Recognizing pathogens by recognizing virulence factor action: the plant immune system.

                        Here’s the PowerPoint show for Lectures 7 and 8.

 

Jones, JDG and JL Dangl (2006) The Plant Immune System. Nature 444, 323-329.

 

Shao, F. et al. (2003) Cleavage of Arabidopsis PBS1 by a bacterial type III effector. Science 301, 1230-1233.

 

Ade J. et al. (2007) Indirect activation of a plant nucleotide binding site–leucine-rich repeat protein by a bacterial protease. Proc. Natl. Acad. Sci., USA 104, 2531-2536.

 

8 W Feb 6         The plant immune system, part 2.

 

                        [Reading assignment as above for Lecture 7.]

 

9 M Feb 11        A broad host pathogen: The Pseudomonas aeruginosa system.

                        SW Chapter 16

                        Here’s the Powerpoint show for Lecture 9

Rahme, L.., et al. (2000) Plants and animals share functionally common bacterial virulence factors. Proc. Natl. Acad. Sci. 97, 8815-8821. (a good review).

Rahme, L.., et al. (1995) Common virulence factors for bacterial pathogenicity in plants and animals. Science 268, 1899-1902. (see also short news article at the end of this pdf.)

 

Extra reading, if interested;

 

He, J. et al. (2004) The broad host range pathogen Pseudomonas aeruginosa strain PA14 carries two pathogenicity islands harboring plant and animal virulence genes. Proc. Natl. Acad. Sci., USA 101, 2530-2535.

 

11 M Feb 18 The Genesis of Cholera epidemics.

 

Here’s the PowerPoint show for Lectures 11 and 12.

 

SW Chapter on Cholera (skim!)

 

Faruque, S. H. and Mekalanos, J. J. (2004) Pathogenicity islands and phages in Vibrio cholerae evolution. Trends Micrbiol. 11, 505-1510.

 

Waldor, M. K. and Mekalanos, J. J. (1996) Science, 272, 1910-1914.

Lysogenic conversion by a filamentous phage encoding cholera toxin.

 

Faruque, S. H. et al. (2004) Genetic diversity and virulence potential of environmental Vibrio cholerae population in a cholera-endemic area.

Proc. Natl. Acad. Sci., USA 101, 2123-2128

 

 

12 W Feb 20 Same as Lecture 11.

 

13 M Feb 25 Intracellular entry, growth and spread: How Salmonella

usurps host cell biology.

 

            Here’s the PowerPoint show for Lecture 13

 

            SW Chapter 26 (skim)

 

Hansen-Wester, I. and Hensel, M. (2001) Salmonella pathogenicity islands

encoding type III secretion systems. Microbes and Infection 3, 549-559.

 

Cirillo, et al. (1998) Macrophage-dependent induction of the Salmonella

pathogenicity island 2 type III secretion system and its role in

intracellular survival. Mol. Microbiol. 30, 175-188.

 

Note: Review the FACS methodology in the Valdivia and Falkow paper from

W Jan 23 first.

     

14 W Feb 27 The battle for your gut: How pathogens trick hosts into helping them in the gut niche.


Here’s the Powerpoint show for Lecture 14

Stecher, B and Hardt, W.-D. (2008) the role of microbiota in infectious
disease. Trends in Microbiology 535, 1-8 epub ahead of print.

Stecher, B. et al. (2007) Salmonella enterica serovar typhimurium
exploits inflammation to compete with the intestinal microbiota. PLoS
Biology 5(10): e244. doi:10.1371/journal.pbio.0050244

[Note: You will need to go to the PLoS Biology web site and download or
study the Supplemental Figures and Tables. This is a good exercise. PLoS
is open source, so you can access it from anywhere]

 

15 M Mar 3 The gut microbiome and gut development.


Here’s the PowerPoint show for Lecture 15 and 16

 

Review Stecher and Hardt minireview from previous lecture

Ley, RE, et al. (2006) Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine. Cell 124, 837–848.

Stappenback, T. S. et al., (2002) Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc. Natl. Acad.
Sci., USA 99, 15451-15455.
 

16 M Mar 5 The gut microbiome and obesity.

 

Ley, RE, et al. (2005) Obesity alters gut microbial ecology. PNAS 102,
11070-11075.

Turnbaugh, PJ, et al., (2006) An obesity-associated gut microbiome with
increased capacity for energy harvest. Nature 444, 1027-1031. (and, at
the end of this pdf is a short research communication from the same
group on humans)

 

March 8-15 Spring Break

 

 

17 M Mar 17 Pathogenesis of Mycobacterium tuberculosis: life inside a macrophage
 

Guest Lecturer, Nathan Rigel, Braunstein Lab, UNC Dept. of Microbiology
and Immunology

Nguyen, L. and Pieters, J. (2005) The Trojan horse: survival tactics of
pathogenic mycobacteria in macrophages. Trends Cell Biology 15, 269-276.

Deghmane, A.-E., et al. (200?) Lipoamide dehydrogenase mediates
retention of coronin-1 on BCG vacuoles, leading to arrest in phagosome
maturation. J. Cell Science 120, 2796-2806.

 

Thursday March 20: Project Outlines due by email to Dr. Dangl by 5pm.

 

18 W Mar 19     Mutualism and glowing squid, 1:

 

                        Here’s the Powerpoint show for Lectures 18 and 19

 

Nyholm, S. and McFall-Ngai, M. J.(2004) The winnowing: Establishing the squid-Vibrio symbiosis. Nature Rev. Microbiol. 2, 632-642.

 

Koropatnick, T. A. et al. (2004). Microbial factor-mediated development in a host-bacterial mutualism. Science 306,1186-1188.

 

 

19 M Mar 24      Mutualism and glowing squid, 2:

 

Lupp, C and Ruby, EG (2005) Vibrio fischeri Uses Two Quorum-Sensing Systems for the Regulation of Early and Late Colonization Factors. J. Bacteriol. 187, 3620-3629.

 

 

20 W Mar 26     Microbial community assembly and host-microbe interactions in the vertebrate intestine

 

Guest Lecturer, Dr. John Rawls, Assistant Professor, Dept. of Cell and Molecular Physiology, UCM-School of medicine

 

Here’s the Powerpoint show for Lectures 20

 

McFall-Ngai, M (2006) Love the One You’re with: vertebrate guts shape their microbiota. Cell127, 247-249.

 

Rawls, JF, et al. (2006) Reciprocal gut microbiota transplants from Zebrafish and Mice to germ-free-recipients reveal host habitat selection. Cell 127, 423-433.

 

 

21 M Mar 31      Mutualism and fungus farming ants I.

 

                        Here’s the Powerpoint show for Lectures 21 and 22

 

Herre, E. A., et al. (1999) The evolution of mutualisms: exploring the paths between conflict and cooperation. Trends in Ecology and Evolution 14, 49-53.

 

Currie, C. R., et al. (1999) Fungus-growing ants use antibiotic-producing bacteria to control garden parasites. Nature 398, 701-704.

 

 

22 W Apr 2        Mutualism and fungus farming ants II

 

Currie, C. R., et al. (2003) Ancient tripartite co-evolution in the Attine ant-microbe symbiosis. Science 299, 386-388.

 

Currie, C. R. et al. (2006) Coevolved crypts and exocrine glands support mutualistic bacteria in fungus-growing ants. Science 311, 81-83.

 

Gerardo, NM et al. (2006) Ancient Host–Pathogen Associations Maintained by Specificity of Chemotaxis and Antibiosis. PLoS Biology 4, 1358-1363.

 

 

 

 

M April 7,W April 9, M April 14    

 

 

NO CLASSES, but TUTORIALS to be scheduled with Dr. Dangl by email. You

must schedule a tutorial.

 

 

For the tutorial, FOCUS on your Research Proposal and Presentation. Read

the course outline for tips. Also, focus on your outline, reading,

preparing a detailed outline and even a rough draft of the Introduction

section. Then prepare your list of experimental aims and predicted

outcomes. Remember to include all necessary control experiments to help

you make your predicted outcomes interpretable.

 

 From March 31-April 15, each of you must schedule with me at least one

30 minute appointment to discuss your progress. Come prepared, bring you

laptop, pdfs of the papers you are using, and outline/current progress.

 

Class presentations (in the order of presentation):

 

 

W April 16