Recommended Readings: Susan Kaech, Ph.D., September 14th

Monday Lecture Series
Monday, September 14th, 2015
4:00 p.m., Carson Family Auditorium (CRC)

Susan Kaech, Ph.D.
Associate Professor of Immunobiology,
Yale School of Medicine
Early Career Scientist,
Howard Hughes Medical Institute

PEPing Up T Cell-mediated Immunity to Viruses and Cancer

Recommended Readings

Empirical Articles

Cui, G., Staron, M. M., Gray, S. M., Ho, P. C., Amezquita, R. A., Wu, J., & Kaech, S. M. (2015). IL-7-induced glycerol transport and TAG synthesis promotes memory CD8+ T cell longevity. Cell, 161(4), 750-761. doi:10.1016/j.cell.2015.03.021.

Laidlaw, B. J., Cui, W., Amezquita, R. A., Gray, S. M., Guan, T., Lu, Y., … & Kaech, S. M. (2015). Production of IL-10 by CD4+ regulatory T cells during the resolution of infection promotes the maturation of memory CD8+ T cells. Nature Immunology, 16(8), 871-879. doi:10.1038/ni.3224

Laidlaw, B. J., Zhang, N., Marshall, H. D., Staron, M. M., Guan, T., Hu, Y., … & Kaech, S. M. (2014). CD4+ T cell help guides formation of CD103+ lung-resident memory CD8+ T cells during influenza viral infection. Immunity, 41(4), 633-645. doi:10.1016/j.immuni.2014.09.007.

Slütter, B., Pewe, L. L., Kaech, S. M., & Harty, J. T. (2013). Lung airway-surveilling CXCR3 hi memory CD8+ T cells are critical for protection against influenza A virus. Immunity, 39(5), 939-948. doi:10.1016/j.immuni.2013.09.013.

Review Paper

Gray, S. M., Kaech, S. M., & Staron, M. M. (2014). The interface between transcriptional and epigenetic control of effector and memory CD8+ T‐cell differentiation. Immunological Reviews, 261(1), 157-168. doi:10.1111/imr.12205.

Kaech, S. M., & Cui, W. (2012). Transcriptional control of effector and memory CD8+ T cell differentiation. Nature Reviews Immunology, 12(11), 749-761. doi:10.1038/nri3307.

Recommended Readings: Joan Strassmann, Ph.D. & David Queller, Ph.D., January 30

Friday Lecture Series
Friday, January 30, 2015
3:45 p.m., Caspary Auditorium

Joan E. Strassmann, Ph.D.
Charles Rebstock Professor of Biology,
Washington University in St. Louis
David C. Queller, Ph.D.
Spencer T. Olin Professor,
Washington University in St. Louis

Altruism, Cheating, and Mutualism in Social Amoebas: Evolution and Mechanisms

Recommended Readings

Brock, D. a, Read, S., Bozhchenko, A., Queller, D. C., & Strassmann, J. E. (2013). Social amoeba farmers carry defensive symbionts to protect and privatize their crops. Nature Communications, 4, 2385. doi:10.1038/ncomms3385

Kuzdzal-Fick, J., Fox, S., Strassmann, J., & Queller, D. (2011). High relatedness is necessary and sufficient to maintain multicellularity in Dictyostelium. Science, 334(6062), 1548–1552. doi:10.3334/ORNLDAAC/797

Stallforth, P., Brock, D. a, Cantley, A. M., Tian, X., Queller, D. C., Strassmann, J. E., & Clardy, J. (2013). A bacterial symbiont is converted from an inedible producer of beneficial molecules into food by a single mutation in the gacA gene. Proceedings of the National Academy of Sciences, 110(36), 14528–14533. doi:10.1073/pnas.1308199110

Strassmann, J. E., & Queller, D. C. (2011). Evolution of cooperation and control of cheating in a social microbe. Proceedings of the National Academy of Sciences, 108 Suppl, 10855–10862. doi:10.1073/pnas.1102451108

Recommended Readings: Wei Yang, Ph.D. March 10

SPECIAL SEMINAR
Monday, March 10, 2014
4:00 p.m., Carson Family Auditorium

Wei Yang, Ph.D.
Senior Investigator and Section Chief
Department of Molecular Biology
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health

Human DNA polymerase η: from Chemistry to Cancer Biology

Recommended Readings:

Empirical Articles

Biertümpfel, C., Zhao, Y., Kondo, Y., Ramón-Maiques, S., Gregory, M., Lee, J. Y., … Yang, W. (2010). Structure and mechanism of human DNA polymerase η. Nature, 465(7301), 1044–1048. doi:10.1038/nature09196

Nakamura, T., Zhao, Y., Yamagata, Y., Hua, Y., & Yang, W. (2012). Watching DNA polymerase η make a phosphodiester bond. Nature, 487(7406), 196–201. doi:10.1038/nature11181

Zhao, Y., Biertümpfel, C., Gregory, M. T., Hua, Y.-J., Hanaoka, F., & Yang, W. (2012). Structural basis of human DNA polymerase η-mediated chemoresistance to cisplatin. Proceedings of the National Academy of Sciences of the United States of America, 109(19), 7269–7274. doi:10.1073/pnas.1202681109

Zhao, Y., Gregory, M. T., Biertümpfel, C., Hua, Y., Hanaoka, F., & Yang, W. (2013). Mechanism of somatic hypermutation at the WA motif by human DNA polymerase η. Proceedings of the National Academy of Sciences of the United States of America, 110(20), 8146–8151. doi:10.1073/pnas.1303126110

Review Papers

Lange, S. S., Takata, K., & Wood, R. D. (2011). DNA polymerases and cancer. Nature Reviews Cancer, 11(2), 96–110. doi:10.1038/nrc2998

Sale, J. E., Lehmann, A. R., & Woodgate, R. (2012). Y-family DNA polymerases and their role in tolerance of cellular DNA damage. Nature Reviews Molecular Cell Biology, 13(3), 141–152. doi:10.1038/nrm3289

Yang, W. (2003). Damage repair DNA polymerases Y. Current Opinion in Structural Biology, 13(1), 23–30. doi:10.1016/S0959-440X(02)00003-9

Recommended Readings: Seth Darst, Ph.D. Monday, Dec. 9

Monday Lecture Series
Structural studies of bacterial transcription: Bacteriophage T7 Gp2 inhibition of Escherichia coli RNA polymerase
Seth Darst, Ph.D.
Jack Fishman Professor
Laboratory of Molecular Biophysics
The Rockefeller University
4:00 p.m., Carson Family Auditorium

Recommended Readings

Review Paper

Samson, J. E., Magadán, A. H., Sabri, M., & Moineau, S. (2013). Revenge of the phages: defeating bacterial defenses. Nature Reviews Microbiology, 11(10), 675–687. doi:10.1038/nrmicro3096

Empirical Articles

Bae, B., Davis, E., Brown, D., Campbell, E. a, Wigneshweraraj, S., & Darst, S. a. (In Press). Phage T7 Gp2 inhibition of Escherichia coli RNA polymerase involves misappropriation of σ70 domain 1.1. Proceedings of the National Academy of Sciences of the United States of America. doi:10.1073/pnas.1314576110

Cámara, B., Liu, M., Reynolds, J., Shadrin, A., Liu, B., Kwok, K., … Wigneshweraraj, S. R. (2010). T7 phage protein Gp2 inhibits the Escherichia coli RNA polymerase by antagonizing stable DNA strand separation near the transcription start site. Proceedings of the National Academy of Sciences of the United States of America, 107(5), 2247–2252. doi:10.1073/pnas.0907908107

James, E., Liu, M., Sheppard, C., Mekler, V., Cámara, B., Liu, B., … Wigneshweraraj, S. (2012). Structural and mechanistic basis for the inhibition of Escherichia coli RNA polymerase by T7 Gp2. Molecular Cell, 47(5), 755–766. doi:10.1016/j.molcel.2012.06.013

Sheppard, C., Cámara, B., Shadrin, A., Akulenko, N., Liu, M., Baldwin, G., … Wigneshweraraj, S. R. (2011). Inhibition of Escherichia coli RNAp by T7 Gp2 protein: role of negatively charged strip of amino acid residues in Gp2. Journal of Molecular Biology, 407(5), 623–632. doi:10.1016/j.jmb.2011.02.013

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.

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.

Predator Phages Competing In The Gut

A team led by Lora V. Hooper, an associate professor of immunology and microbiology at The University of Texas Southwestern Medical Center, and including UT Arlington assistant professor of biology Jorge Rodrigues examined the bacteriophages, or phages, produced by genetic information harbored in the chromosome of the mammalian gut bacterium Enterococcus faecalis. They found that a phage unique to Enterococcus faecalis strain V583 in mice acts as a predator, infecting and harming other similar, competing bacterial strains. They believe these lab results suggest what goes on in the human intestine.

“This organism is using phage as a way to compete in your gut. If the phage is released and gets rid of all the other microbes, then strain V583 will have more nutrients available,” Rodrigues said. “It opens up new questions about the role of phages in the gut system. Ultimately, you could use this as a technique to control bacteria in a natural way.”

The findings were presented in October in the Proceedings of the National Academy of Sciences in a paper called, “A composite bacteriophage alters colonization by an intestinal commensal bacterium.” Other co-authors were members of Hooper’s lab: Breck A. Duerkop, Charmaine V. Clements and Darcy Rollins.

How The Malaria Parasite “Hides” From the Immune System

A research team at the Walter and Eliza Hall Institute has identified one of the crucial molecules that instructs the parasite how to employ its invisibility cloak to hide from the immune system, and helps its offspring to remember how to ‘make’ the cloak.

Research published in the journal Cell Host & Microbe details the first molecule found to control the genetic expression of PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1), a protein that is known to be a major cause of disease during malaria infection.

PfEMP1 plays two important roles in malaria infection. It enables the parasite to stick to cells on the internal lining of blood vessels, which prevents the infected cells from being eliminated from the body. It is also responsible for helping the parasite to escape destruction by the immune system, by varying the genetic code of the PfEMP1 protein so that at least some of the parasites will evade detection. This variation lends the parasite the ‘cloak of invisibility’ which makes it difficult for the immune system to detect parasite-infected cells, and is part of the reason a vaccine has remained elusive.

Project To Develop Metagenomics Tool For Rapid Identification of Microbes

 Battelle Memorial Institute (Columbus, Ohio) announced that it has made an investment of an undisclosed amount in CosmosID for the development of a metagenomics software-based solution for microbial identification.

The investment from Battelle is part of $4 million in financing that CosmosID recently received to support its efforts “to deliver pathogen identification in a single, rapid, and accurate service,” Battelle said, adding that it is partnering with the College Park, Md.-based company to develop and market microbial metagenomics toolkits for public safety and medical treatment applications.

CosmosID’s technology called MetaSeq Genomics uses unassembled reads from next-generation sequencing, probabilistic algorithms, and reference databases to identify pathogens, and antibiotic resistance and virulence factors. The software, which is scalable and updated iteratively, is targeted for diagnostic test development in the markets of public safety and security, medical treatment, environmental monitoring, and drug development, Battelle said.

Privately held CosmosID was founded in 2007 by Rita Colwell, former director of the US National Science Foundation and currently distinguished professor at Johns Hopkins University Bloomberg School of Public Health and the University of Maryland.

Viruses: We’ve Barely Begun To Know Them

Though viruses are the most abundant life form on Earth, our knowledge of the viral universe is limited to a tiny fraction of the viruses that likely exist.  An international team of researchers from the University of Pittsburgh, Washington University in St. Louis, and the University of Barcelona have found that raw sewage is home to thousands of novel, undiscovered viruses, some of which could relate to human health.  Read more about developing new techniques to look for novel viruses in unique places around the world.