The Much Maligned Tick: Key to a New Class of Antibiotics?

Yale researchers have discovered a glycoprotein in ticks (Ixodidae) that kicks in during winter to protect them from the cold also fights infection.  This protein may be the key to a new class of an antibiotics to help  in the battle against dangers pathogens such as MRSA.
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Recommended Readings: Mark M. Davis, Ph.D. April 25

Friday Lecture Series
Friday, April 25, 2014
3:45 p.m., Caspary Auditorium

Mark M. Davis, Ph.D.
Burt and Marion Avery Family Professor of Immunology
Director, Stanford Institute for Immunity, Transplantation and Infection
Member, Bio-X and Stanford Cancer Institute
Stanford University

Reinventing Human Immunology

Recommended Readings:

Davis, M. M. (2008). A prescription for human immunology. Immunity, 29(6), 835–838. doi:10.1016/j.immuni.2008.12.003

Davis, M. M. (2012). Immunology taught by humans. Science Translational Medicine, 4(117), 117fs2. doi:10.1126/scitranslmed.3003385

Kidd, B. a, Peters, L. a, Schadt, E. E., & Dudley, J. T. (2014). Unifying immunology with informatics and multiscale biology. Nature Immunology, 15(2), 118–127. doi:10.1038/ni.2787

Maecker, H. T., McCoy, J. P., & Nussenblatt, R. (2012). Standardizing immunophenotyping for the Human Immunology Project. Nature Reviews Immunology, 12(3), 191–200. doi:10.1038/nri3158

Su, L. F., Han, A., McGuire, H. M., Furman, D., Newell, E. W., & Davis, M. M. (2014). The Promised Land of Human Immunology. Cold Spring Harbor Symposia on Quantitative Biology. doi:10.1101/sqb.2013.78.022905

Recommended Readings: Lora Hooper, Ph.D. April 2

Wednesday, April 2, 2014
4:00 p.m., Carson Family Auditorium

Lora Hooper, Ph.D.
University of Texas Southwestern Medical Center
Investigator, HHMI

Circadian Regulation of Intestinal Immunity

Recommended Readings:

Empirical Articles

Bäckhed, F., Ding, H., Wang, T., Hooper, L. V, Koh, G. Y., Nagy, A., … Gordon, J. I. (2004). The gut microbiota as an environmental factor that regulates fat storage. Proceedings of the National Academy of Sciences, 101(44), 15718–15723. doi:10.1073/pnas.0407076101

Cash, H. L., Whitham, C. V, Behrendt, C. L., & Hooper, L. V. (2006). Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science, 313(5790), 1126–1130. doi:10.1126/science.1127119

Scheer, F. a J. L., Hilton, M. F., Mantzoros, C. S., & Shea, S. A. (2009). Adverse metabolic and cardiovascular consequences of circadian misalignment. Proceedings of the National Academy of Sciences, 106(11), 4453–4458. doi:10.1073/pnas.0808180106

Yu, X., Rollins, D., Ruhn, K. a, Stubblefield, J. J., Green, C. B., Kashiwada, M., … Hooper, L. V. (2013). TH17 cell differentiation is regulated by the circadian clock. Science, 342(6159), 727–730. doi:10.1126/science.1243884

Review Papers

Arjona, A., Silver, A. C., Walker, W. E., & Fikrig, E. (2012). Immunity’s fourth dimension: approaching the circadian-immune connection. Trends in Immunology, 33(12), 607–612. doi:10.1016/

Hooper, L. V, & Macpherson, A. J. (2010). Immune adaptations that maintain homeostasis with the intestinal microbiota. Nature Reviews Immunology, 10(3), 159–169. doi:10.1038/nri2710

Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009). IL-17 and Th17 cells. Annual Review of Immunology, 27, 485–517. doi:10.1146/annurev.immunol.021908.132710

Recommended Readings: Poornima Parameswaran Ph.D. February 10

Monday, February 10, 2014
4:00 p.m., Carson Family Auditorium

Poornima Parameswaran, Ph.D.

Postdoctoral Research Fellow
School of Public Health
University of California, Berkeley

Virome & Immunome Diversity in Dengue & other Infectious Diseases

Recommended Readings:

Empirical Papers

Parameswaran, P., Charlebois, P., Tellez, Y., Nunez, A., Ryan, E. M., Malboeuf, C. M., … Henn, M. R. (2012). Genome-wide patterns of intrahuman dengue virus diversity reveal associations with viral phylogenetic clade and interhost diversity. Journal of Virology, 86(16), 8546–8558. doi:10.1128/JVI.00736-12

Parameswaran, P., Liu, Y., Roskin, K. M., Jackson, K. K. L., Dixit, V. P., Lee, J.-Y., … Fire, A. Z. (2013). Convergent antibody signatures in human dengue. Cell Host & Microbe, 13(6), 691–700. doi:10.1016/j.chom.2013.05.008

Parameswaran, P., Sklan, E., Wilkins, C., Burgon, T., Samuel, M. a, Lu, R., … Fire, A. Z. (2010). Six RNA viruses and forty-one hosts: viral small RNAs and modulation of small RNA repertoires in vertebrate and invertebrate systems. PLoS pathogens, 6(2), e1000764. doi:10.1371/journal.ppat.1000764

Review Articles

Fontana, J. M., Alexander, E., & Salvatore, M. (2012). Translational research in infectious disease: current paradigms and challenges ahead. Translational Research, 159(6), 430–453. doi:10.1016/j.trsl.2011.12.009

Wylie, K. M., Weinstock, G. M., & Storch, G. a. (2012). Emerging view of the human virome. Translational Research, 160(4), 283–290. doi:10.1016/j.trsl.2012.03.006

Recommended Readings: Pardis Sabeti M.D., Ph.D. Friday, Nov 8

Friday, November 8, 2013
3:45 p.m., Caspary Auditorium

Pardis Sabeti M.D., Ph.D.
Senior Associate Member, Broad Institute of MIT and Harvard;
Associate Professor, Center for Systems Biology, Harvard University Department of Organismic and Evolutionary Biology, and Department of Immunology and Infectious Disease at Harvard School of Public Health

Evolutionary Forces in Humans and Pathogens

Recommended Readings:

Empirical Articles

The 100 Genomes Project Consortium. (2010). A map of human genome variation from population-scale sequencing. Nature, 467(7319), 1061–1073. doi:10.1038/nature09534

The International MapMap Consortium. (2005). A haplotype map of the human genome. Nature, 437(7063), 1299–1320. doi:10.1038/nature04226

Grossman, S. R., Andersen, K. G., Shlyakhter, I., Tabrizi, S., Winnicki, S., Yen, A., … Sabeti, P. C. (2013). Identifying recent adaptations in large-scale genomic data. Cell, 152(4), 703–713. doi:10.1016/j.cell.2013.01.035

Sabeti, P. C., Reich, D. E., Higgins, J. M., Levine, H. Z., Richter, D. J., Schaffner, S. F., … & Lander, E. S. (2002). Detecting recent positive selection in the human genome from haplotype structureNature419(6909), 832-837. doi:10.1038/nature01140

Sabeti, P. C., Varilly, P., Fry, B., Lohmueller, J., Hostetter, E., Cotsapas, C., … Gaudet, R. (2007). Genome-wide detection and characterization of positive selection in human populations. Nature, 449(7164), 913–8. doi:10.1038/nature06250

Review Papers

Biswas, S., Akey, J. M. (2006) Genomic insights into positive selection. Trends in Genetics, 22(8), 437-445. doi:10.1016/j.tig.2006.06.005

Kreitman, M. (2000). Methods to detect selection in populations with applications to the human. Annual Review of Genomics and Human Genetics, 1, 539-559. doi: 10.1146/annurev.genom.1.1.539

Nielsen, R., Hellmann, I., Hubisz, M., Bustamante, C., & Clark, A. G. (2007). Recent and ongoing selection in the human genome. Nature Reviews Genetics,8(11), 857-868. doi:10.1038/nrg2187

Sabeti, P. C., Schaffner, S. F., Fry, B., Lohmueller, J., Varilly, P., Shamovsky, O., … & Lander, E. S. (2006). Positive natural selection in the human lineage .Science, 312(5780), 1614-1620. doi:10.1126/science.1124309

Vitti, J. J., Cho, M. K., Tichkoff, S. A., Sabeti, P. C. (2012). Human evolutionary genomics: ethical and interpretive issues. Trends in Genetics, 28(3), 137-145. doi:10.1016/j.tig.2011.12.001

Recommended Readings: Rob Knight, Ph.D. Wednesday, Oct. 30, 2013

Wednesday, October 30, 2013
4:00 p.m., Carson Family Auditorium

Rob Knight, Ph.D.
HHMI Early Career Scientist and Professor
Department of Chemistry & Biochemistry, Department of Computer Science, and BioFrontiers Institute
University of Colorado at Boulder

Gut Microbes and their Role in Malnutrition and Obesity

Recommended Readings:

Review Papers

Clemente, J. C., Ursell, L. K., Parfrey, L. W., & Knight, R. (2012). The impact of the gut microbiota on human health: an integrative view. Cell, 148(6), 1258–1270. doi:10.1016/j.cell.2012.01.035

Gevers, D., Knight, R., Petrosino, J. F., Huang, K., McGuire, A. L., Birren, B. W., … Huttenhower, C. (2012). The Human Microbiome Project: a community resource for the healthy human microbiome. PLoS Biology, 10(8), e1001377. doi:10.1371/journal.pbio.1001377

Hamady, M., & Knight, R. (2009). Microbial community profiling for human microbiome projects : Tools , techniques , and challenges, Genome Research, 19(7), 1141–1152. doi:10.1101/gr.085464.108.19

Ley, R. E., Lozupone, C. a, Hamady, M., Knight, R., & Gordon, J. I. (2008). Worlds within worlds: evolution of the vertebrate gut microbiotaNature Reviews Microbiology6(10), 776–788. doi:10.1038/nrmicro1978

Empirical Articles

Costello, E., Lauber, C., & Hamady, M. (2009). Bacterial community variation in human body habitats across space and time. Science, 326, 8–11.

The Human Microbiome Project Consortium. (2012). Structure, function and diversity of the healthy human microbiome. Nature, 486(7402), 207–14. doi:10.1038/nature11234

Ley, R. E., Bäckhed, F., Turnbaugh, P., Lozupone, C. A, Knight, R. D., & Gordon, J. I. (2005). Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences of the United States of America, 102(31), 11070–5. doi:10.1073/pnas.0504978102

Lozupone, C. A., Stombaugh, J., Gonzalez, A., Ackermann, G., Jansson, J. K., Gordon, J. I., … Knight, R. (2013). Meta-analyses of studies of the human microbiota, Genome Research, 23,1704–1714. doi:10.1101/gr.151803.112

Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., … Gordon, J. I. (2009). A core gut microbiome in obese and lean twins. Nature, 457(7228), 480–484. doi:10.1038/nature07540

Turnbaugh, P. J., Ley, R. E., Mahowald, M. a, Magrini, V., Mardis, E. R., & Gordon, J. I. (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122), 1027–31. doi:10.1038/nature05414

Yatsunenko, T., Rey, F. E., Manary, M. J., Trehan, I., Dominguez-Bello, M. G., Contreras, M., … Gordon, J. I. (2012). Human gut microbiome viewed across age and geography. Nature, 486(7402), 222–7. doi:10.1038/nature11053

Landmark CDC Report Details Threat of ‘Postantibiotic Era’

The Centers for Disease Control and Prevention (CDC) released its “landmark” report today on the rising and lethal threat of antibiotic resistance, titled Antibiotic Resistance Threats in the United States, 2013.

The report describes a complex problem and the steps that must be taken to prevent catastrophic consequences.

In it, experts describe “what happens when the microbes can outsmart our best antibiotics,” explained CDC Director Tom Frieden, MD, MPH, at a press conference. He elaborated by describing his hope that the report will prioritize pathogens and propel action to curb antibiotic resistance.

Recommended Readings: Maria M. Mota PhD March 13, 2013

Special Seminar Series

Malaria Infection, Superinfection and Co-infections: From Simple Models to Complex Interactions

Maria M. Mota,   PH.D.

Unit Leader, Malaria Unit

Instituto de Medicina Molecular

Monday      March 18,  2013

Recommended Readings:

Pinkevych, Mykola; Petravic, Janka; Chelimo, Kiprotich; et al.  2012.  The Dynamics of Naturally Acquired Immunity to Plasmodium falciparum Infection.   PLOS COMPUTATIONAL BIOLOGY.   8(10): e1002729   DOI: 10.1371/journal.pcbi.1002729  

 Klein, Eili Y.; Smith, David L.; Laxminarayan, Ramanan; et al.  2012. Superinfection and the evolution of resistance to antimalarial drugs. PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES.   279( 1743):3834-3842   DOI: 10.1098/rspb.2012.1064  

 Portugal, Silvia; Drakesmith, Hal; Mota, Maria M. 2011. Superinfection in malaria: Plasmodium shows its iron will.  EMBO REPORTS.  12(12):1233-1242    DOI: 10.1038/embor.2011.213  

van Santen, Susanne; de Mast, Quirijn; Swinkels, Dorine W.; et al. 2011.  Hepcidin in malaria superinfection: can findings be translated to humans? NATURE MEDICINE.  17(11):1341-1341   DOI: 10.1038/nm.2488  

 Portugal, Silvia; Carret, Celine; Recker, Mario; et al. 2011.  Host-mediated regulation of superinfection in malaria.   NATURE MEDICINE.  17(6):732-U126    DOI: 10.1038/nm.2368  

 Templeton, TJ; Keister, DB; Muratova, O; et al.  1998. Adherence of erythrocytes during exflagellation of Plasmodium falciparum microgametes is dependent on erythrocyte surface sialic acid and glycophorins.   JOURNAL OF EXPERIMENTAL MEDICINE.  187(10 ):1599-1609   DOI: 10.1084/jem.187.10.1599

NIH Announces Discovery of Promising Drug Target to Prevent S. aureus Infections

ScienceDaily February 10, 2013.   National Institutes of Health (NIH) scientists have identified a promising lead for developing a new type of drug to treat infection caused by Staphylococcus aureus, notable drug-resistant pathogen. They have discovered a transport system for toxins that are thought to contribute to severe staph infections – phenol-soluble modulins (PSMs). The transport system, Pmt, is common to all S. aureus PSMs and critical for bacterial proliferation and disease development in a mouse model. Their experiments suggest that a drug interfering with Pmt’s function could not only prevent production of the PSM toxins, but also directly lead to bacterial death. This research is reported in Nature Medicine.