| Dustin
Brisson |
I am interested in the interactions between pathogenic microbes
and their hosts and how specifically those interactions shape the ecology
and evolution of both the microbe and the host populations. Additionally, I
am interested in the causes and consequences of molecular evolution and
population genetics of pathogens. Methods from field ecology (including
chicken-wire and cargo pants!), advanced molecular techniques, mathematical
modeling, and computational analysis are commonly used in my lab
to address relevant hypotheses. |
| Frederic Bushman |
The Bushman laboratory uses genome-wide analytical methods to study
several problems in host-virus interactions. All of these projects take
advantage of massively parallel DNA sequencing and bioinformatic analysis
of the results. Current projects are as follows:
1) Studies of target site selection by genomic parasites, including retroviruses,
that integrate new copies of themselves in vertebrate genomes.
2) Analysis of the effects of lentivirus infection on the gut microbiota, with
a goal of understanding the GI morbidity associated with HIV infection.
3) Ultra-deep analysis of the nature and consequences of drug resistance mutations
that accumulate during HIV therapy.
4) Development of genetic footprinting methods for characterizing replication
of DNA viruses in tissue culture and in infected hosts. |
| Sara Cherry |
Using genome-wide high-throughput strategies in Drosophila to uncover
host factors involved in viral pathogenesis
The identification and study of host factors involved in viral infection and
replication reveals fundamental insight into cell biological processes and
is critical to overcoming human viral diseases. However, the study of host-virus
interactions has been hampered by the dearth of host-pathogen systems amenable
to genetic screening, and lack of in vivo animal models suitable for rigorously
characterizing interactions between the virus and host. To address these issues,
we have developed novel, high-throughput approaches that combine functional
genomics with bioinformatics in the model organism Drosophila, to define and
characterize host factors that regulate pathogenesis—including both factors
hijacked by the virus for replication, as well as those used by the host to
combat the viral invader. Genome-wide RNAi screens coupled with forward genetics
in adult flies make this model organism ideal for unbiased interrogation of
cellular factors central to pathogenesis. Indeed, we have infected /Drosophila/
cells with viruses from diverse viral families of central importance to human
disease. Due to the variety of our query pathogens, our analyses are likely
to uncover a broad range of replicative requirements and host counter-measures.
Through these investigations, we will gain a comprehensive understanding of
the interplay between host and pathogen in a complex and dynamic setting, including
identification of common subversion strategies and unique adaptations of individual
pathogens. |
| Fevzi
Daldal |
Bacterial proteomics and evolution of extracytoplasmic proteins with
a focus on the links between cytochromes, disulfide bond formation proteins
and related periplasmic proteases. |
| Doron
Greenbaum |
Malaria is a devastating global disease causing at least 500 million
clinical cases and more than 1 million deaths each year. The completed
genome of P. falciparum is a rich resource in the search for
targets of novel antimalarial therapies and allows the possibility of
more systematic approaches to therapeutic discovery and design. In particular,
the P. falciparum genome codes for a predicted 100 putative proteases
representing all five classes: cysteine, metallo, aspartyl, threonine
and serine, suggesting a complex role for proteases in parasite development.
Genomic and proteomic technologies have begun to address the challenge of assigning
functions to the numerous proteins encoded by the multitude of sequenced prokaryotic
and eukaryotic genomes. In particular, I believe chemical strategies for proteome
analysis will become increasingly more important to enable functional characterization
and profiling of enzyme activity on a global scale. My laboratory is focusing
on developing and exploiting new technologies at the interface between biology
and chemistry to globally study how proteases function in the malarial parasite.
We have developed a new technique termed activity-based protein profiling which
uses small molecule inhibitors as chemical proteomic probes (ABPs) to study
protease function. We will use this technique as well as quantitative proteomics,
genomics, recombinant protein expression, and molecular genetics in order to
better understand proteolytic systems. |
| Beatrice Hahn |
Origin and evolution of human pathogens in Africa
|
| Sridhar Hannenhalli |
Our lab focuses on computational methods to decipher transcriptional
regulation. The specific problems include pol II promoter prediction,
cis element identification and predicting transcriptional modules that
coordinately regulate a group of transcriptionally related genes. We are
also interested in the evolution and population variations of transcriptional
regulation, at the level of transcription factor genes, their expression
and their cis elements. |
| Scott Hensley |
Our lab studies viral immune escape mechanisms. Most of our studies
focus on how influenza viruses accumulate mutations in antibody binding
sites of viral surface proteins, a process termed 'antigenic drift'. Using
a mouse model, we have found that a major driving force of influenza virus
antigenic drift is related to how the virus interacts with cellular receptors
rather than how the virus interacts with individual antibodies. Future
projects will address if these mechanisms are utilized by diverse subtypes
of influenza virus as well as other groups of viruses. |
| Junhyong Kim |
The Kim lab is engaged in computational and functional genomics research,
broadly asking evolutionary questions across several different systems.
The systems that we work in are natural strains of yeast and mammalian
brain cells. We have been investigating the evolution of gene regulatory
dynamics and molecular processes that establish cellular phenotype. In
particular, we are interested in measuring and modling single-cell variability
in genome-wide RNA levels. We also have a long standing interest in computational
problems related to phylogenetics and population genetics. We develop
algorithms, statistical models, and mathematical models, as well as single-cell
genomics techniques. Some of the example questions are, "how does
molecular timing such as gene expression evolve?", "what are
the molecular determinants of a cell's phenotype and what are its architectural
properties?", "what kind of evolutionary processes can be inferred
from empirical data?", "what is the role of endogenous viral
elements in mammalian genome function?". |
| Rahul Kohli |
Pathogen resistance to antimicrobials; pathogen escape from immune recognition
by antigenic variation |
| Mike Levy |
My group works at the interface of epidemiology, ecology and statistics
to understand and control vector-borne and other infectious diseases.
We have focused our research the past five years on the control of urban
Chagas disease transmission in Peru. Our research team in Peru conducts
epidemiological studies on Chagas disease as well as entomological and
ecological research on disease vectors and reservoirs. In addition the
team uses quantitative and qualitative methods to elucidate the factors
that have led to urbanization of a disease traditionally associated
with rural poverty. My methodological interests include developing new
Bayesian methods to retrace the history of epidemics, and applying techniques
from control theory to optimize interventions against infectious diseases. |
| Joshua Plotkin |
I am broadly interested in molecular population genetics and evolution.
My research is based largely on computation and mathematical theory. A
primary goal is to develop statistical methods for inferring the action
of natural selection from intra-specific polymorphism data and from inter-specific
sequence variation. Of particular interest are applications to the genomes
of pathogens, whose proteins experience a wide range of selective pressures
determined by interactions with their hosts. |
| Mecky
Pohlschröder |
Evolution and Diversity of Protein Translocation
Protein secretion across hydrophobic membranes is an essential cellular process
in all organism. Transport of the prokaryotic secretome (including virulence
factors, polymer degrading enzymes and subunits of cell-surface structures,
among others) mainly occurs via the universally conserved Sec- and twin arginine
translocation (Tat) pathways. Using a combination of proteomic and genomic
approaches, we study both pathways in archaea and bacteria to better understand
the evolution of protein transport and to reveal the significance of the
diverse use of the Sec and Tat machineries. For high-throughput in silico
secretome analysis, we also develop bioinformatics tools (see: http://SignalFind.org)
that predict different classes of Sec and Tat substrates and thus allow us
to ask intriguing questions such as: i) what are the selective pressures
for secreting certain substrates in a folded conformation via the Tat pathway,
rather than via the Sec pathway, which secretes proteins in an unfolded conformation
and ii) why is the Tat pathway used to such varying extents among prokaryotes.
Considering the fact that the Tat pathway is a potential antibiotic target
(eukaryotic Tat-component homologs have only been identified in chloroplasts)
answers to basic questions like these are also highly biomedically relevant. |
| David Roos |
Studies in the Roos focus on protozoan parasites in the
phylum Apicomplexa, including Plasmodium (which causes malaria), and Toxoplasma
(a prominent source of congenital neurological birth defects, and an opportunistic
pathogen associated with AIDS and other immunosuppressed conditions).
The large number of parasite genome sequences now available provides one
of the most attractive systems for research in comparative genomics. As
deep-branching eukaryotes that are amenable to experimental manipulation
in the laboratory, these organisms also offer insights into the origins
and evolution of eukaryotic organelles, including novel targets for drug
development. |
| Paul Sniegowski |
My laboratory studies experimental and natural microbial populations
with the general goal of connecting evolutionary and ecological processes
to causes and consequences at the molecular genetic level. Three broad
areas of research are active within my laboratory: 1) the evolution and
evolutionary significance of mutation rates and mutational phenomena;
2) the genetic and ecotypic structure of natural microbial populations;
and 3) evolutionary and ecological genomics. Research in the first area
utilizes experimental populations of Escherichia coli, experimental
and natural populations of Saccharomyces cerevisiae and its sympatric
sister species S. paradoxus, and computer simulation approaches.
Research in the second and third areas focuses on natural populations
of S. cerevisiae and S. paradoxus. |
| Jeff Weiser |
The Weiser lab examines the pathogenesis of bacterial infection involving
the respiratory tract. Most studies have focused on two pathogens, Streptococcus
pneumoniae (the pneumococcus) and Haemophilus influenzae, which commonly
infect humans and are the major causes of bacterial diseases involving
the airway. A particular interest of the group is in defining the molecular
events involved in colonization of the mucosal surface-the first step
in the pathogenesis of disease. This approach has involved genomic analysis
of both bacterial and host genes whose expression is affected by colonization.
Genomic analysis using microarray technology has been carried out with
in vitro models using respiratory epitheial cells in culture and in vivo
using a mouse model of colonization. |
| Jun (Jay) Zhu |
Vibrio cholerae exist naturally in various aquatic reservoirs
and causes the severe disease cholera. It is capable of quorum sensing;
a system with which V. cholerae can monitor bacterial concentrations
and subsequently modulate their genetic expression. Our laboratory has
identified various stressful environmental conditions where the functionality
of quorum sensing strongly influences the survival of V. cholerae.
These data indicate that quorum sensing plays a role in survival of V.
cholerae in environmental reservoirs, an important part of the epidemic
cycle of this pathogen. We are currently using genomic and proteomic techniques
to characterize the effect of various environmental conditions on the
survival of quorum sensing mutants, as well as examine the prevalence
of quorum sensing evolution in newly isolated pathogenic and environmental
strains. Understanding the role quorum sensing plays in the survival and
transition from a marine environment to hosts via potable water is key
to understanding the impact this system has on survival in the environment
and ultimately the infection of the human host. |
