The 2009 ICAAC Young Investigator Awards  recognize and reward five early-career scientists  for their research excellence and potential in  microbiology and infectious diseases. Since  1983, two awards have been supported by an  unrestricted educational grant from Merck, U.S.  Human Health Division, while two are sponsored  by ASM. In 2007, an additional award  from Merck, U.S. Human Health Division, was  added to recognize excellence in HIV research.  Tobias M. Hohl and Xiaorong Lin are the 2009  laureates for the Merck-sponsored awards, and  Angelika Gründling and Anton Y. Peleg are the  2009 laureates for the ASM-sponsored awards.  David Masopust is the 2009 laureate for the  Merck-sponsored award for HIV research.    
 
Tobias M. Hohl is honored for his research on  the interaction of Aspergillus fumigatus and the  pulmonary innate immune system. Hohl earned  his M.D.-Ph.D. from the tri-institutional program  of Weill Medical College and Graduate  School of Medical Sciences of Cornell University,  Memorial Sloan-Kettering Cancer Center,  and Rockefeller University, New York. While a  Research Fellow at Memorial Sloan-Kettering  Cancer Center, Hohl studied chemokine induction  and signaling pathways in macrophages  exposed to A. fumigatus. He learned that Dectin-1, a receptor expressed on dendritic cells and macrophages, binds β-glucans on the surface of  germinating A. fumigatus conidia. Hohl showed  that β-glucans are expressed in state-specific  fashion on germinating A. fumigatus, thereby  restricting the inflammatory response to germinating  but not dormant fungal spores. His work  demonstrated for the first time how the mammalian  immune system recognizes Aspergillus infections;  it was published in PLoS Pathogens.   

 Hohl continued his work by investigating the  effect of echinocandin antifugals on the exposure  of β-glucans on the surface of A. fumigatus  conidia and hyphae. His research demonstrated  that caspofungin and micafungin decrease  β-glucan exposure on conidia but significantly  increase β-glucan exposure on hyphae, resulting  in a significantly increased inflammatory response  of macrophages and dendritic cells. Published  by the Journal of Infectious Diseases,  Hohl's research suggests that echinocandin activity  against invasive mold infections may be  attributable, at least in part, to augmented innate  inflammatory responses.    

Hohl is currently Assistant Professor, Vaccine  and Infectious Diseases Institute, Fred Hutchinson  Cancer Research Center, and Assistant Professor,  Division of Allergy and Infectious Diseases,  University of Washington, Seattle. He was  nominated by Lawrence Corey of Fred Hutchinson  Cancer Research Center.    

Xiaorong Lin is honored for her work on Cryptococcus  neoformans, an opportunistic fungal  pathogen. Lin received her Ph.D. from the University  of Georgia and completed her postdoctoral  fellowship at Duke University Medical  Center. She is currently an Assistant Professor,  Department of Biology, Texas A & M University,  College Station.    

C. neoformans has a defined sexual cycle with  two mating types. In nature and clinical isolates,  one mating type (α) predominates. Lin's work  provided evidence for a modified form of the  sexual cycle involving only one mating type,  suggesting that the population can undergo sexual  recombination despite the predominance of  only one mating type. This work implies that  recombination can produce spores with greater  genetic diversity and can have profound effects  on how pathogenic characteristics appear in a  population. Her discovery of same-sex mating  was published by Nature in 2005 with Lin as the  first author with further evidence published in  PLoS Genetics in 2007 and PLoS Pathogens in  2009, also with Lin as the first author.    

Lin established her lab at Texas A & M in  2008 where she finalized and published, in Infection  and Immunity, her work on the role of  mating type and ploidy in the virulence of Cryptococcus.  Her first independent studies describing  the use of agrobacterium as a transkingdom  mutagenesis tool for Asperigillus fumigatus and  showing that pigment mutants are highly virulent  in a heterologous host model system have  been published in PLoS One.    

Lin was nominated by Matthew S. Sachs of  Texas A & M University.    

Angelika Gründling, Assistant  Professor, Imperial  College London, is  honored for her work on  the role of lipoteichoic  acids in cell envelope assembly  in Staphylococcus  aureus.    

Gründling's initial work  focused on how the  lambda holin, protein S,  sits in the membrane and  how S monomers interact. She constructed a library  of single-Cys mutants and performed chemical  modifications on membrane preparations containing  the variant S proteins while looking for  protected domains to define the transmembrane  domains of the holin. Gründling showed that the S protein has three TM domains. She went on to use  her large collection of single-Cys mutants in numerous  ways-using oxidative conditions to force  disulfide bond formation, mapping the interaction  surfaces of the TM domains, and demonstrating  unambiguously that the inhibitor form of the S  holin acts by dimerizing with the effector form.    

Holins accumulate in the membrane during  the infective cycle and as they accumulate, there  is an increasing drainage of protons across the  bilayer. At some point, the cell's ability to resist  drainage is exceeded and the potential collapses.  This allows concerted hole formation by all the  holins in the membrane. Gru¨ ndling researched  the proportionality between motility and the  membrane potential to see if holins were timed  by this mechanism. Her work resulted in the  filming of bacteria swimming and suddenly  stopping and exploding with no hint of a decreased  motility leading up to lysis. It was evidence that holins do not titrate out the membrane  potential but rather, have no effect on the  energization of the membrane until the holes are  formed. This work was published in Proceedings  of the National Academy of Sciences and  was chosen as Science's Editor Choice.    

Gründling received both her B.S. and her  Ph.D. from the University of Vienna, Austria,  and completed postdoctoral training at the  Harvard Medical School and the University of  Chicago. She was nominated by Liz Sockett,  Institute of Genetics, University of Nottingham,  United Kingdom.    

Anton Y. Peleg is recognized  as an expert on  the clinical impact, epidemiology,  and management  of infections due to  multidrug-resistant gramnegative  bacteria, specifically  Acinetobacter. Peleg  completed his medical  degree at Monash University  Medical School  and his residency at the  Alfred Hospital, Melbourne, Australia, where  he provided the first description of carbapenemase  genes in Australia. He designed phenotypic  methods for their detection in gram negative  organisms.    

Peleg went on to complete a clinical research  fellowship at the University of Pittsburgh Medical  Center, followed by a fellowship at Massachusetts  General Hospital, Beth Israel Deaconess  Medical Center, Harvard Medical School,  where he currently is a Research Fellow. During  this time, he has been working on prokaryoteeukaryote  interactions identified using the Caenorhabditis  elegans model. Peleg's work has  shown the antagonistic interaction between  Acinetobacter and Candida, pathogens that frequently  coinhabit patients. Specifically, when C.  elegans is coinfected with these organisms, the  pathogenicity of Candida albicans is attenuated  because of the ability of Acinetobacter to prevent  filament formation in C. albicans.    

Peleg has developed a coinfection screen assay in C. elegans and an Acinetobacter baumannii  mutant library to assess within this assay the  identification of molecular mechanisms responsible  for the interaction. These tools helped Peleg  identify a gene, known as the gacS-like sensor  kinase gene, in A. baumannii. It seems that  this gene is critically important for virulence  regulation in other gram-negative bacteria, but  it has not been described in A. baumannii.    

Currently, Peleg aims to characterize further  the molecular interactions between Acinetobacter  and Candida and determine if the virulence  toward C. albicans is representative of  virulence toward mammals. He is also working  on the mechanism of A. baumannii growth inhibition  by farnesol, a C. albicans quorum-sensing  molecule. He was nominated by Eleftherios  Mylonakis of Massachusetts General Hospital.    

David Masopust, Assistant Professor, University  of Minnesota, Minneapolis, is honored for  his significant contributions to our understanding  of T cell memory. Masopust's primary interest  is understanding immunological memory of  bacterial and viral pathogens at mucosal surfaces  and applying it to designing effective vaccines  against mucosal pathogens.    

While earning his Ph.D. at the University of  Connecticut, Farmington, Masopust became interested  in the lab's studies of understanding  CD8 T cell immune responses in the intestinal  mucosa. His first publication examined the mucosal  response to a systemic viral infection  which suggested that functional differences existed  between lymphoid and nonlymphoid CD8  memory T cells.    

Masopust continued his work by analyzing  the CD8 T cell response in lymphoid and  nonlymphoid tissues. Masopust and his colleagues  studied the primary and memory response  to vesicular stomatitis virus and Listeria  infections. They demonstrated that CD8  memory T cells in the nonlymphoid tissues  retained effector levels of target cell killing  activity while lymphoid memory cells exhibited  low cytotoxic activity. This landmark  study transformed the field of immunological  memory and helped establish a new paradigm  in memory T cell biology.    

During his postdoctoral fellowship at Emory  University, Masopust's published worked showed  that effector CD8 T cells and memory T cells are  able to migrate pervasively in the body irrespective  of their tissue of origin and elucidated the  properties of memory CD8 T cells within the  intestinal mucosa and the relationship between  T cell differentiation state and their history of  exposure to multiple stimulations by bacteria and viruses that share cross-reactive T cell  epitopes.    

Masopust's recent work shows that a heterologous  prime boost strategy could elicit extraordinarily  high levels of memory cytotoxic T lymphocytes  in mice. He is currently collaborating  to see if it can be adapted to immunizing and  protecting macaques from a vaginal challenge  with simian immunodeficiency virus.    

Masopust was nominated by Rafi Ahmed,  Emory Vaccine Center, and a Fellow of the  American Academy of Microbiology.