CIHMID Postdoctoral Fellows Program Potential Projects

The following is a list of potential projects in CIHMID host labs that prospective applicants to the CIHMID Postdoctoral Fellows Program could use as a basis for initiating contact with potential hosts.

Applicants are not required to choose a project from this list. Novel projects that are not on this list can be proposed, and applicants may apply to work with host labs who are not actively listing projects on this page.

This list will be continuously updated as new prospective projects arise.

 

Opportunistic pathogens can subvert infection barriers (e.g., host immune functions and nutrient limitations) and switch from peaceful commensal to potentially lethal pathogen. The factors promoting either outcome are unknown, but must be shaped by dynamic physiological interactions between host and pathogen. This project aims to determine key factors at the host-pathogen interface that mediate the switch between controlled and acute infection in the Drosophila systemic infection model and the opportunistic human pathogen Serratia marcescens. Since we approach this problem at multiple scales, we are looking for potential candidates with a diverse set of backgrounds. Experience in fly immunology, physiology, fly and bacterial cell biology or genetics, as well as bacterial pathogenesis is beneficial, but there is also room for quantitative approaches (mathematical modeling). This project is a collaboration of the Lazzaro, Ellner, Buchon and Dörr labs.

 

Tobias Dörr and Lars Westblade (Weill Cornell Medicine) Labs: Mechanisms and Clinical Significance of β-Lactam Tolerance in Gram-negative Pathogens
Antibiotic treatment failure is an increasingly widespread burden on human health that poses one of the most significant threats to planetary life. Treatment failure is often due to the development of antibiotic resistance. A complete comprehension of the factors that promote the development, and particularly the dissemination, of antibiotic resistance is still lacking. Nonetheless, evidence suggests that antibiotic “tolerance” – the ability of a microorganism to sustain viability for extended time periods in the presence of antibiotics – is an important stepping stone towards frank resistance. This project, a collaborative effort between the Dörr Laboratory in Ithaca, and the Westblade Laboratory at Weill Cornell Medicine in NYC, is focused on β-lactam tolerance in nosocomial Gram-negative pathogens such as Klebsiella pneumoniae and Enterobacter cloacae. Using a diverse toolset encompassing genetic, biochemical and clinical microbiology methods, we will interrogate the metabolic state and the genetic circuitry underlying β-lactam tolerance in clinically important Gram-negative pathogens. Furthermore, we will probe the connection between tolerance and the development of overt β-lactam resistance (e.g., acquisition of β-lactamases, which are enzymes that degrade β-lactams). Ultimately, we hope to uncover novel targets for antitolerance agents that could serve as adjuvants to improve the efficacy of β-lactam antibiotics, which are among our most important antibiotics.

 

Nicolas Buchon, and Praveen Sethupathy Labs: Molecular dialogue between Intestinal Stem Cells and Microbiota 
The intestinal epithelium faces unique challenges as it is constantly exposed to the passage of ingested material including food, bacteria and xenobiotics. To maintain tissue function, the intestinal epithelium is undergoing continuous renewal mediated by intestinal stem cells (ISCs). ISC proliferation and differentiation are constantly adapted both to the microbes present and to the gut environment, suggesting that the structure and composition of the gut epithelium is plastic. Sustained tissue function is essential to organismal health and disruption of gut homeostasis is associated with a broad range of pathologies such as inflammatory disorders and cancer. Despite the central role of ISCs in health and disease, little is known about the molecular mechanisms that regulate ISC activity in response to the microbial environment in the luminal content and how these processes sustain health. Recent results in the Buchon lab have demonstrated that indigenous and invasive gut microbes influence ISC activity. Notably, we have demonstrated that pathogens and non-pathogenic microbes influence the differentiation of ISCs in an opposite way. This project is a collaboration between the Buchon and Sethupathy labs, in which we propose to dissect the molecular dialogue between ISCs and the microbiota using both Drosophila melanogaster and mouse enteroids as models. 

 

Andrew Moeller Lab: Evolution of Symbiosis
The
 Moeller Lab studies the evolution of symbiosis between animals and microorganisms. Our current work focuses on vertebrates’ co-evolutionary histories with bacteria through a combination of -omics approaches, gnotobiotic and microbiology experiments, and natural history. We are recruiting highly motivated and independent postdoctoral candidates with training in genomics, population genetics, microbiology, immunology, or related fields. Candidates interested in the genetic basis of microbial adaptation to host immune systems, the modes and genetics of microbial transmission within and among host lineages, the genetic basis of host adaptation to microorganisms, or other topics pertaining to the evolutionary causes and consequences of host-microbe relationships are particularly encouraged to apply.

 

Adam Bogdanove and Miguel Pineros Labs: Evolution of Symbiosis
The long-term goals served by this project are mechanistic understanding of plant disease and development of broadly effective and durable means of control. The project seeks to structurally and functionally characterize a pathogen-activated host gene that plays a critical role in disease in a major crop species, and to ascertain the potential of strategies to interfere with activation or function of the gene to prevent disease development. As the gene is predicted to function in nutrient transport, the project aims to shed light on the broader question of how nutrients may regulate pathogenesis in plants. The project will further benefit society through mentoring, education, and public outreach that will increase participation by members of underrepresented groups and engage and inform the public. 

 

Nicolas Buchon, and Laura Harrington Labs: Mosquito Gut Regenerative Response to Pathogenic Invasion
Mosquitoes cause 400,000 malaria deaths and transmit viruses to hundreds of millions. The vectorial capacity of mosquitoes depends on their ability to survive infection. The damaging effects of pathogenic invasion of the mosquito midgut are well-documented, but little is known about hos mosquitoes tolerate this stress. Intestinal stem cell (ISC) mediated midgut epithelial repair, is essential for Drosophila survival following oral ingestion of pathogens. The mosquito midgut epithelium contain ISC-like cells, but their functional significance for infection outcomes and mosquito survival is unknown. We propose to address this knowledge gap in vector biology by investigating the mosquito gut regenerative response to pathogenic invasion. This collaboration between the Buchon and Harrington labs will aim at characterizing gut epithelial cell dynamics in mosquitoes under conditions of homeostasis and oral infection, and determine the mechanisms that underlie tissue repair in the mosquito midgut, and its influence on vectorial capacity. 

 

Corrie Moreau Lab: Host-microbe interactions
The Moreau Lab studies the evolution of symbiosis between animals and their diverse microbial communities. Current work focuses on the benefits of microbial communities for ant hosts from nutrient provisioning to contributions to cuticle formation. Methods include amplicon sequencing, quantification, metagenomics, functional assays, experimental manipulations, and more. This work is deeply rooted in natural history and understanding organismal biology. Our multidisciplinary team addresses questions about the role of symbiosis in the ecology and evolution of ant hosts and opportunities exist for project related to these areas.

 

John Parker and Iwijn De Vlaminck Labs: Evolution of RNA Viruses
Fast evolving RNA viruses, such as rotavirus, influenza virus, human immunodeficiency virus, and zika virus, are a leading cause of death worldwide and represent a major challenge for global disease control. Despite their small genome size, often comprised of only a few thousand nucleotides and a handful of genes, it remains exceedingly difficult to study the infection biology of RNA viruses using modern gene sequencing technologies. The De Vlaminck (Dept. of Biomedical Engineering) and Parker (Dept of Microbiology & Immunology) labs are focused on developing and using novel single-cell sequencing technologies to understand the evolutionary forces operating at the level of single cells that select RNA virus genotypes. The extreme heterogeneity of RNA virus infections is difficult to survey with current molecular technologies which are largely limited to analyzing populations of infected cells. To overcome this limitation, we have recently created a single cell RNA sequencing technology that combines multiplexed amplicon sequencing with single cell transcriptional profiling: Droplet Assisted RNA Targeting by single-cell Sequencing (DART-seq). With DART-seq it is possible to catalog the diversity of viral genome sequences within single infected cells, and at the same time record the cellular response to viral infection. The cost per-cell of DART-seq is less than one dollar, and a single DART-seq assay can yield measurements across thousands of cells in a biological sample. In proof-of-principle studies, we have used DART-seq to profile viral-host interactions and viral genome dynamics in single cells infected with mammalian orthoreovirus (REOV) strain Type 3 Dearing (T3D). Future experiments will  expand upon these initial technology development experiments to interrogate the infection biology of REOVs and other segmented RNA viruses including rotavirus, a common cause of gastroenteritis, and influenza A virus. We also plan to further develop the DART-seq approach as a tool to allow assessment of single-cell viral replication and recombination. This project provides the opportunity for a postdoctoral associate to develop new scRNA-seq technologies optimized for the study of RNA virus biology.

Hector Aguilar-Carreno Lab: Mechanisms of Virus-Host Interactions
The main focus of our research program is to elucidate key mechanistic components in enveloped viruses and their target host cells that: 1] mediate viral entry into cells, 2] elicit cell immune responses, and 3] mediate viral egress from cells. Within our lab, these studies lead to the design, development, and testing of novel antiviral agents and vaccines. Among the enveloped viruses, we focus a significant portion of our efforts on the deadly and zoonotic Nipah and Hendra viruses, but are also interested in other emerging and zoonotic viruses including influenza virus. Our highly multi-disciplinary approaches include: basic biochemistry, molecular and cellular biology, omics, organic chemistry, and animal model studies. We are interested in highly-motivated post-doctoral candidates proposing projects that explore host-virus interactions using these or other multidisciplinary approaches.

Stephen EllnerNicolas Buchon and Brian Lazzaro:  Systems dynamics of stochastic infection outcomes in Drosophila
A central question in infection biology is to understand why two individuals exposed to the same pathogen may have life-versus-death differences in outcome. Host or pathogen heterogeneity is a natural explanation, but even when this is drastically constrained (genetically identical hosts reared together, identical infection protocols) we have found that many bacterial pathogens in Drosophila melanogaster have bimodal outcomes, with some hosts dying at high bacteria burden while others survive indefinitely with a persistent but fairly asymptomatic infection. We have previously constructed a conceptual model, based on experimental results, wherein pathogen proliferation rate and timing of host immune response interact to determine the outcome (Duneau et al, eLife 2017;6:e28298). We now seek a quantitative biologist to develop and test process-based system dynamics models to understand mechanistically when and how bimodal outcomes can be robust across a wide region of parameter space. Modeling should be complemented by theoretical and empirical study of host immune kinetics and bacterial behavior, to identify which processes govern the dynamics and outcome of the host-pathogen interaction.

 

Ilana Brito Lab: Exploring host-microbe interactions related to metabolic disorders      The Brito Lab is recruiting postdocs in direct host-microbiome interactions that may modulate health. We are specifically interested in exploring bacterial proteins that can alter host cellular functions. We are looking for individuals with either computational or wet lab experience, or both. Interested candidates will be able to explore the mechanistic underpinnings of microbiome-related disorders through molecular biology techniques, cell culture, and mouse models. We’re looking for motivated individuals who want to work in this fast-moving field. 

 

Cynthia Leifer and David Putnam Labs: Development of broadly neutralizing antibodies to influenza using a novel bacterial outer membrane vesicle platform
The Leifer and Putnam labs have an ongoing collaboration to use innovative engineering techniques develop, test, and understand the underlying immunological mechanisms of new vaccine adjuvant bacterial outer membrane vesicle platforms. We are interested in postdoctoral candidates proposing to take a cross-disciplinary approach to vaccine and adjuvant development, and animal model testing. The collaboration between the Putnam and Leifer labs is supported by a recently awarded NIH R01, but the candidate can propose related projects that take advantage of the expertise in both labs. Experience in the following techniques is preferred, but not required: microbiology, molecular biology, small animal models, and immune response assays.

Tory Hendry Lab: Bacteria-Host Interactions
The Hendry lab uses experimental, molecular evolutionary, and -omics approaches to understand the impact of host interactions on bacterial ecology and evolution. Research in the lab focuses on a variety of systems, including insect and plant associated bacteria and bioluminescent symbionts in marine fish. Our interdisciplinary group encompasses broad interests within microbiology, evolution, and ecology and opportunities exist for projects related to these areas.

 

Angela Poole Lab: Effects of diet on the gut microbiome
The Poole Lab studies the effects of diet on the gut microbiome. We want to know why individuals respond differently to the same dietary perturbations. Our resources include, but are not limited to, a human metabolic research unit to help facilitate running studies with human participants, a mouse facility and experience running germ free mouse experiments, and a technology core for sequencing of all kinds. We would love to host a postdoctoral fellow with experience in studying physiology using mouse models, bioinformatics, computational biology, or microbial anaerobes. Prior firsthand experience accompanied by a publication record are required.

 

Teresa Pawlowska and Gillian Turgeon Labs: Understanding fungal innate immunity
The goal of this project is to elucidate mechanisms of innate immunity in early-diverging soil fungi Mucoromycotina. Unlike other filamentous fungi, Mucoromycotina encode few genes for secondary metabolite biosynthesis and do not synthesize extracellular antibacterial secondary metabolites that suppress antagonistic microbes. Instead, they appear to respond to bacterial antagonists by mounting a potent reactive oxygen burst and altering their cell wall composition, which prevents bacterial entry into fungal hyphae. The project is a collaboration between two SIPS scientists, a symbiosis expert Teresa Pawlowska and a fungal geneticist Gillian Turgeon. How antagonistic bacteria are recognized by the fungus and how this information is transduced to elicit its defensive responses are the two main questions to be addressed in the course of the project.