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Syllabus and Reading Assignments.doc Syllabus and Reading Assignments.doc Document Transcript

  • SYLLABUS (5/18/05 version) Pathobiology 552: Cell Biology of Pathogens and their Hosts Spring Quarter 2004 Tuesday & Thursday 11:00-12:50 (Health Sciences Bldg., Rm, T-474) Course Organizer: Jaisri Lingappa, M.D., Ph.D. Teaching Assistant: Julia Dooher Class email account: Class website: Primary Text: Molecular Biology of the Cell, 4th Ed (Alberts, Johnson, Lewis et al.) Garland Science 2002 Other Texts: Molecular Cell Biology, 4th & 5th Eds (Lodish, Berk, Zipursky et al.) W.H. Freeman & Co 1999 Cellular & Molecular Immunology, 5th Ed (Abbas, Lichtman & Pober) Saunders 2003. The Cell: A Molecular Approach, 3rd Ed (Cooper). ASM Press, 2000. Cellular Microbiology (Cossart, Boquet, Normark, & Rappuoli). ASM Press, 2000. Principles of Virology 2nd Ed (Flint, Enquist, Krug, Racaniello, Skalka). ASM Press, 2000. All texts are on reserve at the Health Sciences Library, shelved by call number. You can access these by following the course reserves link, In order to use links provided below you must be using a UW computer or logged into your personal computer under your UW account. Guest Lecturers: Caroline Cameron, PhD; Patrick Duffy, MD; Nancy Freitag, PhD; Denise Galloway, PhD; Nancy Haigwood, PhD; Renee LeBoeuf, PhD; Conrad Liles, MD PhD; David Sherman, PhD. Grant Review Sessions: Lingappa/Sherman You will be notified by email when there are updates to the syllabus, and they will be posted on the class website: Lecture Title & Lecturer Reading Assignments & Learning Objectives & Date (e-mail address) 1 Translocation and Post- A. Required textbook chapters: Alberts, Ch. 6, 335-365 and Ch. 12, p. 689-706. Tue translational Modifications B. Recommended review: Schnell JD, Hicke L. Non- March 29 Jaisri Lingappa, M.D., Ph.D. traditional functions of ubiquitin and ubiquitin-binding proteins. J Biol Chem. 2003 Sep 19;278(38):35857-60. Dept. of Pathobiology LINK: C. Required primary paper for discussion: None. The first discussion session will be a review/discussion of (Updated 2005) “Techniques in Cell Biology”. Come prepared to ask questions and explain methods such as immunoprecipitation, immunofluorescence co-localization, immunogold labeling, epitope tagging, cellular fractionation, immunoblotting, pulse chase labeling, and in vitro systems. D. Learning objectives: 1. How do cytosolic chaperones function in protein biogenesis? 2. Describe the events of ER translocation and what is unique about the ER environment? 3. How do ER chaperones function? 4. What is ERAD? 5. Describe how proteins undergo N-glycosylation. 6. Describe different categories of acylation. 2 Intracellular Trafficking: ER A. Required textbook chapters: Alberts, Ch. 13, p. 711- 746; Ch.13, p. 756-65. Th to Golgi to Lysosome 1
  • March 31 Jaisri Lingappa, M.D., Ph.D. B. Recommended review: Mellman, I. and G. Warren. The Road Taken: Past and Future Foundations of Membrane Traffic. Dept. of Pathobiology Cell 100: 99-112 (2000). This review presents a historical and conceptual overview of vesicular trafficking. LINK: Click to go to article (Updated 2005) C. Required primary paper for discussion: Cholera toxin is exported from microsomes by the Sec61p complex. Schmitz, A. et al. J. Cell Bio. 148: 1203-12 (2000). LINK: Click to go to article D. Learning objectives: 1. How is topology conserved in the secretory pathway? 2. How is protein topology assessed experimentally? 3. What molecular mechanisms are involved in ER to Golgi trafficking and lysosomal sorting? 4. What experimental systems have been used to study trafficking? 5. Describe different coat proteins and the role of adaptors. 6. Describe mechanisms by which viruses utilize and exploit the trafficking machinery of the cell 3 Nuclear Trafficking A. Required textbook chapter: Alberts, Ch. 12, p. 659-678. B. Required literature review: Pemberton LF, Paschal BM. Tue Jaisri Lingappa, M.D., Ph.D. Mechanisms of receptor-mediated nuclear import and nuclear Apr 5 Dept. of Pathobiology export. Traffic. 2005 Mar;6(3):187-98. LINK: http://www.blackwell- (Updated 2005) C. Required primary paper for discussion: Yedavalli VS, Neuveut C, Chi YH, Kleiman L, Jeang KT. Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function. Cell. 2004 Oct 29;119(3):381-92. LINK: uid=PIIS0092867404008360 Comment in Cullen BR. Human immunodeficiency virus: nuclear RNA export unwound. Nature. 2005 Jan 6;433(7021):26-7. LINK: file=/nature/journal/v433/n7021/full/433026a_fs.html D. Learning objectives: 1. What is the function of the nuclear pore? 2. What is the structure of the nuclear envelope and the nuclear pore? 3. What is an NLS and an NES? What role do they play in the replication of pathogens, such as viruses? 4. What proteins regulate nucleocytoplasmic transport and how do they act? 5. What experimental systems have been used to study nuclear transport? 4 Plasma Membrane and A. Required textbook chapters: Alberts, Ch. 10 p. 583- 599; and Ch. 12, p. 746-756. Th Receptors B. Recommended literature review: Regulated portals of entry 2
  • Apr 7 Jaisri Lingappa, M.D., Ph.D. into the cell. Conner, S. D. and Schmid, S. L. Nature 422: 37 (2003). LINK: Click to go to article OR Dept. of Pathobiology file=/nature/journal/v422/n6927/abs/nature01451_fs.html&dyno ptions=doi1112814416 (Updated 2005) C. Required primary paper for discussion: Pelkmans, L., J. Kartenbeck, and A. Helenius. Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nat. Cell Biol. 3: 473 - 483 (2001). LINK: file=/ncb/journal/v3/n5/full/ncb0501_473.html&filetype=pdf D. Learning objectives: 1. What are the functions of the plasma membrane? 2. What are the phospholipid and protein components of the plasma membrane? 3. What are the key features of clathrin-mediated endocytosis, caveolar uptake and ubiquitin-mediated endocytosis? 4. What machinery and mechanisms are involved in fusion of vesicles to the plasma membrane? 5. Describe how viruses usurp endocytosis machinery. Th OPTIONS FOR PRESENTATION SESSION I DISTRIBUTED TO STUDENTS Apr 7 5 The Extracellular Matrix and A. Required textbook chapters: Alberts, Ch. 19, p. 1065-1070, and p. 1090-1118). Tue Junctions B. Required primary paper for discussion: Apr 12 Caroline Cameron, Ph.D. He Y. W. et al. The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens. Nat. Dept. of Medicine Immunol. 5:88-97 (2004). LINK: Click to go to article OR Comment in McDonald C. and Nunez, G. Mindin the fort. Nat. (Updated 2005) Immunol. 5:16-18 (2004). LINK: Click to go to article OR C. Learning objectives: 1. What are cell junctions? 2. What is the extracellular matrix (i.e. structure, functions, components, distribution)? 3. Understand how extracellular matrix components can be used by pathogens as a route of attachment AND how extracellular matrix components can serve as an integral part of the innate immunity. 6 Trafficking to and Function of A. Required textbook chapter: Alberts, Ch. 12, p. 678-688. B. Required review: Cooke BM, Lingelbach K, Bannister LH, 3
  • Th Other Organelles Tilley L. Protein trafficking in Plasmodium falciparum-infected red blood cells. Trends Parasitol. 2004 Dec;20(12):581-9. Apr 14 Jaisri Lingappa, M.D., Ph.D. LINK: Direct link to paper won’t work. Please click following Dept. of Pathobiology link to go to journal page. C. Required primary paper for discussion: Klemba M, Beatty (Updated 2005) W, Gluzman I, Goldberg DE. Trafficking of plasmepsin II to the food vacuole of the malaria parasite Plasmodium falciparum. J Cell Biol. 2004 Jan 5;164(1):47-56. LINK: D. Learning objectives: 1. Describe similarities and differences in mitochondria, chloroplast, peroxisome, and apicoplast origins and structure. 2. Compare and contrast trafficking of proteins into mitochondria, chloroplasts, peroxisomes, and apicoplasts, 3. Describe signals, machinery, and energetics involved in translocation into different organelles. Th STUDENTS TURN IN PREFERENCES FOR PRESENTATION SESSION I Apr 14 7 Cytoskeleton and Motility A. Required reading: Lodish, Molecular Cell Biology, pp. 752-768. Actin assembly dynamics. Tue Nancy Freitag, Ph.D. B. Recommended review: Gouin E, Welch MD, Cossart P. Apr 19 Dept. of Pathobiology Actin-based motility of intracellular pathogens. Current Opinion in Microbiology 8: 35 – 45 (2005). (Overview of pathogen exploitation of actin assembly). LINK: (Updated 2005) cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1569485 5 C. Required primary paper for discussion: Jeng RL et al. A Ricettsia WASP-like protein activates the Arp2/3 complex and mediates actin-based motility. Cellular Microbiology 6: 761 – 769 (2004). LINK: genre=article&sid=nlm:pubmed&issn=1462-5814&date=2004& volume=6&issue=8&spage=761 E. Learning objectives: 1. What regulates the shape and assembly of the cell cytoskeleton? 2. How do pathogens exploit host cell actin assembly? Tue FIRST TAKE-HOME EXAM GIVEN OUT Apr 19 (Tue April 19 – Tue April 26) 8 Attachment and Invasion A. Required literature reviews: 4
  • Th Nancy Freitag, Ph.D. 1. Torres AG et al. Adherence of diarrheagenic Escherichia coli strains to epithelial cells. Infect. Immun. 73: 18 – 29 (2005). Apr 21 Dept. of Pathobiology This paper will be used as an overview of the myriad adhesive strategies used by one bacterial species. LINK: (Updated 2005) 2. Bacterial invasion: the paradigms of enteroinvasive pathogens. Science 304: 242 – 248 (2004). Nice overview of invasive strategies of several different pathogens. LINK: B. Required primary paper for discussion: Perrin AJ et al. Recognition of bacteria in the cytosol of mammalian cells by the ubiquitin system. Current Biology 14: 806 – 811, (2004). uid=PIIS0960982204002829 C. Learning objectives: 1. How do pathogens attach to cells? 2. How do pathogens enter host cells? 3. How do pathogens survive once they are inside of a host cell? 4. How do host cells detect cytosolic intruders? 9 Bacterial Protein Secretion A. Required background reading: (1) Mori H, Ito K. The Sec protein-translocation pathway. Tue David Sherman, Ph.D. Trends Microbiol. 9(10):494-500 (2001). Apr 26 Dept. of Pathobiology Use PubMed Link cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1159745 (Updated 2005) 1 (2) Pallen MJ, Chaudhuri RR, Henderson IR. Genomic analysis of secretion systems. Curr Opin Microbiol. 2003 Oct;6(5):519-27. LINK: cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1457254 6 B. Required primary paper for discussion: Guinn KM, Hickey MJ, Mathur SK, Zakel KL, Grotzke JE, Lewinsohn DM, Smith S, Sherman DR. Mol Microbiol. 51(2):359-70 (2004). Individual RD1-region genes are required for export of ESAT-6/ CFP-10 and for virulence of Mycobacterium tuberculosis. I’d like to use this paper as a starting point for a discussion of question 4 below. LINK: cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1475677 8 C. Learning Objectives: 1. How does general protein secretion work in prokaryotes? 2. What modifications to the general scheme are present in bacterial pathogens? 3. In what ways does protein secretion contribute to bacterial pathogenesis? 4. How might one investigate the possible presence of a new secretion system? 5
  • Tue FIRST TAKE-HOME EXAM TURNED IN (Tue April 19 – Tue April 26) Apr 26 10 Cell Division and Pathogens A. Required textbook chapter: Alberts , Chapter 17, p. 983- 1010. Th Denise Galloway, Ph.D. B. Required literature review: Apr 28 FHCRC Sherr CJ, Roberts JM. Living with or without cyclins and cyclin-dependent kinases. Genes Dev. 2004. Nov 15;18(22):2699-711. (Updated 2005) C. Required primary paper for discussion: Chen W et al. Identification of specific PP2A complexes involved in human cell transformation. Cancer Cell. 2004 Feb;5(2):127-36. uid=PIIS1535610804000261 D. Learning Objectives: 1. Learn the basic mechanisms of cell cycle control. 2. Learn how the DNA virus oncoproteins deregulate the p53 and Rb pathways. 3. Learn how the DNA virus oncoproteins block apoptosis. 4. Learn the mechanisms underlying cellular senescence, immortality, transformation and tumorigenicity. PRELIMINARY GRANT PROPOSAL AIMS DUE! 11 Cell Death and Pathogens A. Required background reading: 1. Hengartner MO. The biochemistry of apoptosis. Nature; 407: Tue Conrad Liles, M.D., Ph.D. 770-776 (2000). May 3 _fs.html (Updated 2005) 2. Savill J and Fadok V. Corpse clearance defines the meaning of death. Nature 407, 784 - 788 (2000). _fs.html 3. Edinger AL and Thompson CB. Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol. 2004 Dec;16(6):663-9. cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1553077 8 B. Recommended background reading (optional): 1. Reed JC. Mechanisms of apoptosis. Am J Pathol Reed 157 (5): 1415. 2. Fink SL, Cookson BT. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun. 2005 Apr;73(4):1907-16. 6
  • view=long&pmid=15784530 3. Badley, A. Mechanisms of HIV-associated lymphocyte apoptosis Blood 96: 2951 (2000). For those interested in HIV pathogenesis: 4. Textbook chapter: Alberts, ch. 17, p. 1010-1025. C. Required primary papers for discussion: 1. Chan F K-M. A Role for Tumor Necrosis Factor Receptor-2 and Receptor-interacting Protein in Programmed Necrosis and Antiviral Responses. J. Biol. Chem., Vol. 278, Issue 51, 51613-51621, (2003). LINK: 2. Kondo T, et al. Essential roles of the Fas ligand in the development of hepatitis. Nature Med 3:409-413 (1997). This paper is not online; copies will be brought to class. D. Learning objectives: 1. What is apoptosis (programmed cell death)? 2. What mechanisms are used for removal of apoptotic cells? 3. What assays are used to detect apoptotic cells? 4. How do caspases participate in extrinsic and intrinsic pathways? 5. How is apoptosis regulated? 6. What are the major biological roles for apoptosis? Th PRESENTATION SESSION I May 5 12 Signaling Overview A. Required textbook chapters: Alberts, ch. 15, p. 831-899. B. Recommended review: Pawson, T. Specificity in signal Tue Jaisri Lingappa, M.D., Ph.D. transduction: from phosphotyrosine-SH2 domain interactions to May 10 Dept. of Pathobiology complex cellular systems. Cell 116:191-203 (2004). LINK: uid=PIIS0092867403010778 (Updated 2005) C. Optional review: Martin, G. The hunting of the Src. Nature Rev. Mol. Cell Bio. 2:467-475 (2001). LINK: cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1138947 0 This review presents a historical overview of the discovery of basic concepts in signaling from a scientist who played a critical role in the field. D. Required primary paper for discussion Balabanian K, Harriague J, Decrion C, Lagane B, Shorte S, Baleux F, Virelizier JL, Arenzana-Seisdedos F, Chakrabarti LA. CXCR4-tropic HIV-1 envelope glycoprotein functions as a viral chemokine in unstimulated primary CD4+ T lymphocytes. J Immunol. 2004 Dec 15;173(12):7150-60. LINK: E. Learning objectives: 1. Describe different categories of signaling and different types of cell surface receptors. 7
  • 2. How do G protein-coupled receptors act? 3. Describe the signal transduction pathway of receptor tyrosine kinases. 4. What are second messengers? 5. Discuss examples of how signaling is used by pathogens. 13 TLR Signaling and Disease A. Required review: Beutler B, Hoebe K, Du X, and Ulevitch RJ. How we detect Th Julia Dooher (TA) microbes and respond to them: the Toll-like receptors and their May 12 Dept. of Pathobiology transducers. J Leukocyte Biology 74(4):479-85. Alberts, ch. 15, p. 831-899. (Updated 2005) B. Recommended review (commentary on discussion paper): Jean-Luc Imler & Jules A. Hoffmann. Toll signaling: the TIReless quest for specificity. Nat Immunol. 2003 Feb;4(2):105-6. C. Required primary paper for discussion Oshiumi et al. Nature Immunology 4, 161 - 167 (2003) TICAM-1, an adaptor molecule that participates in Toll-like receptor 3−mediated interferon beta induction E. Learning objectives: 1. Describe different types of toll-like receptors and their cognate ligands 2. Understand the basics of TLR signaling pathways (MyD88-dependent and MyD88-independent), and the importance of adaptors for defining specificity. 3. Describe how the TLRs shape the adaptive immune response, and how this may lead to disregulation of adaptive response. Th OPTIONS FOR PRESENTATION SESSION II DISTRIBUTED TO STUDENTS May 12 14 Pathogens and Antigen A. Required literature review: Chow AY, Mellman I. Old lysosomes, new tricks: MHC II Tue Presentation dynamics in DCs. Trends Immunol. 2005 Feb;26(2):72-8. May 17 Jaisri Lingappa, M.D., Ph.D. LINK: Dept. of Pathobiology cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1566812 1 B. Recommended literature review: (Updated 2005) Rescigno, M. Dendritic cells and the complexity of microbial infection. Trends in Microbiol. 10: 425-31 (2002). LINK: cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1221750 8 C. Required primary paper for discussion: 8
  • Delamarre L, Holcombe H, Mellman I. Presentation of exogenous antigens on major histocompatibility complex (MHC) class I and MHC class II molecules is differentially regulated during dendritic cell maturation. J Exp Med. 2003 Jul 7;198(1):111-22. LINK: D. Learning Objectives: 1. Learn types of dendritic cells and their functions. 2. How are responses to dendritic cells modulated? 3. What cell biologic events occur during dendritic cell maturation? 4. How do pathogens interfere with antigen presentation? Tue STUDENTS TURN IN PREFERENCES FOR PRESENTATION SESSION II May 17 15 Cell Biology and A. Required literature review: Th Immunology of Theofilopoulos AN, Dummer W, Kono DH. T cell homeostasis May 19 Inflammation and systemic autoimmunity. J Clin Invest. 2001 Aug;108(3):335-40. Renee LeBoeuf, Ph.D. Dept. of Pathobiology Gianani R, Eisenbarth GS. The stages of type 1A diabetes: 2005. Immunol Rev. 2005 Apr;204:232-49. (Updated 2005) B. Required primary papers for discussion: King C, Ilic A, Koelsch K, Sarvetnick N. Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell. 2004 Apr 16;117(2):265-77. uid=PIIS0092867404003356 Commentary: Gallego AM and Bevan MJ. Driven to autoimmunity: the nod mouse. Cell 2004, 117(2):149-51 uid=PIIS009286740400340X C. Learning Objectives: 1. What is autoimmunity? 2. What molecular mechanisms are involve? 3. What experimental systems are used to study autoimmunity? 4. Could pathogens be involved? 5. How to invoke tolerance? Th GRANT PROPOSALS DUE May 19 16 Host Response to Parasites A. Required reading: Abbas Chapter 15: Immunity to Microbes Tue Patrick Duffy, M.D. (This text is on reserve in the Health Sciences Library) May 24 Dept. of Pathobiology B. Recommended review articles: 1. Zambrano-Villa, S. et al., How protozoan parasites evade 9
  • the immune response. Trends Parasitol. 18:272 (2002). cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12 036742&query_hl=4 2. Stevenson MM, Riley EM.Innate immunity to malaria. Nat Rev Immunol. 2004 Mar;4(3):169-80. Review. LINK: file=/nri/journal/v4/n3/abs/nri1311_fs.html&dynoptions =doi1116488414 C. Required primary papers for discussion & commentary: 1. Bull PC, et al. Plasmodium falciparum-infected erythrocytes: agglutination by diverse Kenyan plasma is associated with severe disease and young host age. 2000. J Infect Dis. 182: 252-9. 00107/000107.html 2. Commentary relevant to #1primary article: Bull PC, Marsh K The role of antibodies to Plasmodium falciparum-infected-erythrocyte surface antigens in naturally acquired immunity to malaria. 2002 Trends Microbiol. 10:55-8. cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11827 798&query_hl=10 2. Ocana-Morgner, C. et al. Malaria blood stage suppression of liver stage immunity by dendritic cells. J Exp Med;197(2):143 (2003). cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12538 654&query_hl=12 D. Learning objectives: 1. Describe the major mechanisms by which protozoan pathogens evade immunity, including antigenic variation, parasite localization, and modulation of immune cells. 2. Explain how P. falciparum uses the variant antigen PfEMP1 to evade exposure to host immunity. 3. Explain how malaria parasites modulate dendritic cell function in order to suppress stage-specific protective immune responses by the host. 4. Give examples of parasite molecules or processes that inhibit or subvert host antibody- or complement-mediated protective immunity. 17 Host Response to Viruses A. Required textbook chapters: Flint SJ et al. Principles of Virology: Chapters 14 (review), 15 Th Nancy Haigwood, Ph.D (This text is on reserve in the Health Sciences Library) May 26 Dept. of Pathobiology B. Recommended Review articles: Johnson, W. E., and R. C. Desrosiers. 2002. Viral persistance: HIV’s strategies of immune system evasion. Annu Rev Med 53:499-518. (Updated 2005) An excellent review on how HIV evades the immune system. 10
  • The mechanisms, concepts are applicable to other viruses as well. cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=118 18487&query_hl=2 C. Required primary papers for discussion: 1. Chackerian B, Rudensey LM, Overbaugh J. Specific N- linked and O-linked glycosylation modifications in the envelope V1 domain of simian immunodeficiency virus variants that evolve in the host alter recognition by neutralizing antibodies. J Virol. 1997 Oct;71(10):7719-27. view=reprint&pmid=9311856 2. Schlender et al. Inhibition of toll-like receptor 7- and 9- mediated alpha/beta interferon production in human plasmacytoid dendritic cells by respiratory syncytial virus and measles virus. J Virol. 2005 May;79(9):5507-15. view=long&pmid=15827165 3. Wei X et al. Antibody neutralization and escape by HIV-1. Nature. 2003 Mar 20;422(6929):307-12. 70_fs.html D. Learning Objectives: 1. What are the major mechanisms used by viruses to evade innate and adaptive immunity? 2. What is the association between types of viral infection (acute and chronic infection) and modulation of immune responses? 3. How does HIV trick the various arms of the immune system? 4. What are the major methods used to measure adaptive immunity? Tue Jaisri Lingappa May 31 PRESENTATION SESSION II and Julia Dooher AND SECOND TAKE-HOME EXAM GIVEN OUT (Tue May 31 – Tue June 7) Proposal Session I/A: David Sherman Students will be assigned to ONE proposal review session (either A, B, or C). Reviews, and Julia Dooher 11
  • Session A held in T-478, 4:30-6:10 pm Bring your proposal reviews to class. Reviews, Wed. June 8 Proposal Session II/B: Jaisri Students will be assigned to ONE proposal review session (either A, B, or C). Reviews, Lingappa Session B held in T-474, 4:30-6:10 pm Bring your proposal reviews to class. Reviews, Wed. June 8 Proposal Session III/C: Jaisri Students will be assigned to ONE proposal review session (either A, B, or C,). Reviews, Lingappa and Julia Dooher Session C held in T-474, 4:30-6:10 pm Bring your proposal reviews to class. Reviews, Wed. June 8 12