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Research Opportunities

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Prospective Students

The goal of the NIH Oxford-Cambridge (OxCam) Scholars Program is to create, foster, and advance unique and collaborative research opportunities between NIH laboratories and laboratories at the University of Oxford or the University of Cambridge. Each OxCam Scholar develops a collaborative research project that will constitute his/her doctoral training. Each Scholar also select two mentors – one at the NIH and one in the UK – who work together to guide the Scholar throughout the research endeavor.

Students may select from two categories of projects: Self-designed or Prearranged. OxCam Scholars may create a self-designed project, which enables students to develop a collaborative project tailored to his/her specific scientific interests by selecting one NIH mentor and one UK mentor with expertise in the desired research area(s). Alternatively, students may select a prearranged project provided by NIH and/or UK Investigator(s) willing to mentor an OxCam Scholar in their lab.

Self-designed Projects 
Students may create a novel (or de novo) project based on their unique research interests. Students have the freedom to contact any PI at NIH or at Oxford or Cambridge to build a collaboration from scratch. The NIH Intramural Research Program (IRP) represents a community of approximately 1,200 tenured and tenure-track investigators providing a wealth of opportunity to explore a wide variety of research interests. Students may visit https://irp.nih.gov to identify NIH PIs performing research in the area of interest. For additional tips on choosing a mentor, please visit our Training Plan.

Prearranged Projects
Investigators at NIH or at Oxford or Cambridge have voluntarily offered collaborative project ideas for NIH OxCam Scholars. These projects are provided below and categorized by research area, NIH Institute/Center, and University. In some cases, a full collaboration with two mentors is already in place. In other instances, only one PI is identified, which allows the student to select a second mentor to complete the collaboration. Please note that prearranged project offerings are continuously updated throughout the year and are subject to change.

26 Search Results

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646
Category:
Microbiology and Infectious Disease
Project:

Engineering the microbiota to reduce the spread of antibiotic resistance

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
UK Mentor:

Prof. Mathew Stracy

University:
Oxford
Project Details:

Antibiotics are crucial for the treatment of bacterial infections, but they can also cause significant collateral damage to the microbiota (de Nies et al. Nat Rev Microbiol. 2023). Antibiotics supress the growth of commensal microorganisms and at the same time select for drug-resistance. Individuals are often benignly colonized with resistant potential pathogens persisting at low levels within their microbiota, such as extra-intestinal pathogenic Escherichia coli (ExPEC). Antibiotics can lead to overgrowth of these resistant pathogens, facilitating their spread within and between individuals (Stracy et al. Science. 2022).Antibiotics can also lead to resistance genes spreading between bacteria within the microbiota through various horizontal gene transfer (HGT) mechanisms.

This overall aim of this project is to answer the important questions:

  1. What are the key factors that determine the level of antibiotic-induced resistance overgrowth/spread within the microbiota?
  2. How does antibiotic-induced pathogen overgrowth and level of HGT differ between individuals?
  3. Can we engineer the microbiota to prevent the spread of resistance?
     

To achieve this, we will use experimental approaches with synthetic and human-derived microbial communities as well as developing microscopy methods to understand the effect of antibiotics on the micro-scale biogeography of the microbiota. We will test approaches to modify the members of the microbiota to minimize antibiotic-induced pathogen overgrowth or HGT.

641
Category:
Microbiology and Infectious Disease
Project:

Characterizing structures of human monoclonal antibodies against novel P. falciparum blood-stage antigens

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
NIH Mentor:

Dr. Joshua Tan

University:
Oxford
Project Details:

Monoclonal antibodies have emerged in recent years as powerful tools to guide vaccine design and potentially to directly prevent infectious disease. Plasmodium falciparum, which causes malaria, is a relatively unexplored pathogen in this area, with only a few major vaccine candidates dominating the field despite the thousands of proteins expressed by the parasite. This project aims to isolate, characterize and determine the structures of human monoclonal antibodies against known and novel P. falciparum blood-stage antigens using cutting-edge technology. This collaborative project combines the expertise of the Tan lab in isolating human monoclonal antibodies against infectious pathogens and the expertise of the Higgins lab in solving crystal structures of antibody-antigen complexes to identify new sites of vulnerability on parasites at high resolution.

624
Category:
Microbiology and Infectious Disease
Project:

Population genomics and sequencing methodologies in host-pathogen systems

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
NIH Mentor:

Dr. Elodie Ghedin 

UK Mentor:

Dr. John Lees

University:
Cambridge
Project Details:

Potential subprojects include: Extending methods for pangenome annotation and analysis to eukaryotic pathogens (e.g. https://www.biorxiv.org/content/10.1101/2023.01.24.524926v1).

Developing adaptive sampling and hybrid enrichment techniques for pathogen/bacteria/host sequencing (see https://www.nature.com/articles/s41587-022-01580-z.)  

Linking strain/variant transmission with pathogen
genetic determinants and host epidemiology. (see: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552050/ and https://www.science.org/doi/full/10.1126/scitranslmed.abg4262)

471
Category:
Microbiology and Infectious Disease
Project:

Hepatic schistosomiasis and HIV interactions: Epidemiological approaches to pathogenesis and clinical targets

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
NIH Mentor:

Dr. Irini Sereti

University:
Oxford
Project Details:

Globally, HIV and schistosomiasis are leading causes of death due to infectious diseases. Despite available interventions, the infections remain uncontrolled in low-income settings causing acute and chronic morbidities. Intestinal schistosomiasis is caused by a parasitic blood fluke, most commonly of the species Schistosoma mansoni, and is predominantly found in sub-Saharan Africa. Chronic infections lead to advanced disease including liver fibrosis, portal hypertension, upper gastrointestinal tract bleeding, and severe anaemia. In the context of coinfections, severe clinical outcomes including death may be likely due to immune failure, interactions related to general fibrosis, and responses to starting antiretroviral therapy. In this project, you will have the opportunity to work with cutting-edge statistical and big data approaches alongside state-of-the art immunology to examine disease progression in the context of schistosome and HIV coinfections in arguably some of the poorest settings worldwide.

The group of Associate Prof. Chami studies schistosomiasis evaluating transmission, clinical outcomes, and treatment strategies, especially for liver fibrosis, in the SchistoTrack Cohort with the Uganda Ministry of Health. This Cohort is the largest individual-based cohort tracking individuals prospectively in the context of schistosomiasis. At Oxford, students can get exposure to computational, big data approaches to clinical epidemiology and field experience in global health research.

The group of Dr. Sereti studies HIV immune pathogenesis with a focus on inflammatory complications related to HIV and coinfections. Studies on biomarkers and how they may assist in identifying early people with HIV who may develop inflammatory and other adverse complications is currently an active area of investigation in the lab as they can also inform disease pathogenesis and new targeted interventions.

At the NIH, students can get experience in immunology research (wet lab) with optional exposure to complicated cases within a clinical setting.

 

470
Category:
Microbiology and Infectious Disease
Project:

Schistosomiasis pathogenesis from mice to humans

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
NIH Mentor:

Dr. P'ng Loke

University:
Oxford
Project Details:

There is a pressing need to improve the understanding of morbidity for schistosomiasis. These parasitic blood flukes afflict over 250 million people worldwide with over 700 million people at risk. For Schistosoma mansoni (a species that causes the intestinal form of schistosomiasis), untreated individuals can develop severe or functional morbidities such as enlarged livers/spleens, periportal fibrosis, oesophageal varices, anaemia, and chronic gut inflammation. The onset and progression of these morbidities is a complex interplay of host genetics and immune response, environmental factors, coinfections, and social determinants. This project is an exciting opportunity to combine work in immunology with epidemiology, providing opportunities to apply computational approaches, experimentally test mechanistic hypotheses found in humans in mice, and gain fieldwork experience in global health research. The candidate will gain skills in both wet lab work and fieldwork in Uganda. You will join multidisciplinary labs at the NIH-NIAID and Oxford.

460
Category:
Microbiology and Infectious Disease
Project:

Examining gut bacteria and bacterial pathogens to identify species combinations to prevent or treat disease

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
UK Mentor:

Prof. Kevin Foster

University:
Oxford
Project Details:

The human microbiome is important for many aspects of our health and yet we currently lack the ability to modulate it for the vast majority of diseases. The key challenge is that it is a diverse ecological system, containing many strains and species of microbe, which needs new approaches and paradigms for the treatment of disease. This project will culture diverse anaerobic species of gut bacteria alongside bacterial pathogens to look for species combinations that can prevent or treat disease. The core methods will involve bacterial culture in the lab, but also germ-free mouse work to validate discoveries. A combination of ecological and evolutionary approaches will be applied to help rationally design multispecies communities that both treat disease but also avoid the evolution of resistance in pathogens. In this way, the goal is to help usher in a new set of treatments for microbiome-based diseases and reduce our reliance on antibiotics.

 

445
Category:
Microbiology and Infectious Disease
Project:

Characterising antibiotic-induced collateral damage in the gut microbiome

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
UK Mentor:

Prof. Mathew Stracy

University:
Oxford
Project Details:

Antibiotics help clear an ongoing infection, but they can also cause significant collateral damage: they select for drug-resistant strains and cause dysbiosis to the commensal gut microbiota. This antibiotic-induced selection for resistance within the microbiome can facilitate the spread of resistant pathogens to extra-intestinal infections and to other patients (see our recent work: Stracy et al. Science. 2022, 375 (6583), 889-894).

This project will aim to understanding how antibiotics cause collateral damage to the microbiota leading to subsequent resistant infections. This will involve experiments with synthetic and human-derived microbial communities as well as developing microscopy methods to understand the effect of antibiotics on the micro-scale biogeography of the microbiota. The aim is to characterise the key factors that determine how antibiotics affect a patient’s resident microbial population and cause resistant opportunistic pathogens to spread. This will be used to help develop new ways to minimize the spread of antibiotic resistance both within and between patients. The project would suit applicants with a strong background in microbiology and keen interest in developing new ways to combat antibiotic resistance.

439
Category:
Microbiology and Infectious Disease
Project:

Establishing the role of low level systemic pathogens in Chronic disease

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
UK Mentor:

Prof. Karl Morten

University:
Oxford
Project Details:

It is becoming clear that the human microbiome extends beyond the gut with bacteria and fungi found in our cells and tissues. In a range of chronic diseases, evidence is emerging that combinations of pathogens are involved in disease.  Myalgic Encephalomyelitis/Chronic fatigue (ME/CFS), Chronic Lyme disease (CLD) and PANS/PANDAS have been linked to the presence of currently unknown pathogens. In CLD and PANS/PANDAS patients antibiotic treatments have been shown to improve symptoms. In ME/CFS raised levels of anti-microbial peptides, increased gut permeability and elevated levels of antibodies raised against specific bacteria have been found in blood. Data from our collaborator SoftCell biologicals indicates that high levels of wall less bacteria (L-Forms) can be cultured from blood, with high numbers of pathogens also detected by deep sequencing.

In this project we will examine blood samples of PANS/PANDAS, ME/CFS, CLD and healthy controls using metagenomic sequencing approaches. L-Form cultures will be established and subjected to anti-pathogen agents. Cell lines will be infected with L-Form organisms and thoroughly characterised using Raman microscopy and assays of mitochondrial function/dynamics. Oxford studies have shown that peripheral blood mononuclear cells from individuals with ME/CFS, multiple sclerosis and healthy controls are very different. Mitochondria also directly interact with parasites. Anti-pathogen agents and drugs which modulate mitophagy will be tested to determine if they can enhance the clearance of pathogens. The impact of Oxidative phosphorylation, glycolysis and different fuels on mitochondrial pathogen clearance will be investigated.

430
Category:
Microbiology and Infectious Disease
Project:

Investigating the evolutionary trajectories of P. aeruginosa

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
UK Mentor:

Prof. Martin Welch

University:
Cambridge
Project Details:

“Life will find a way….” In a now famous quote from the 1993 movie Jurassic Park, the “chaotician” Ian Malcolm nicely captures the essence of adaptation through evolution. But series evolutionary change often requires multiple mutations to arise – the changes arising from SNPs and indels in single genes usually amount to little more than phenotypic “tinkering”. So what would happen if we could “step on the evolutionary gas pedal” and accelerate the pace of change? Or alternatively, what would be the consequences of “slamming on the evolutionary brakes” to prevent adaptation? Well, these are just the kind of approaches that we have developed in the Welch lab, and we are applying these to look at how the opportunistic bacterial pathogen, Pseudomonas aeruginosa, adapts to the presence of infection-relevant selection pressures. Essentially, we’ve engineered the mismatch-repair system to come under the control of an inert chemical inducer, and so can “rheostatically” modulate the rate of mutation from very high (1000 x the wild-type level) to very low indeed (eliciting a state of “hypomutation” in which evolutionary change essentially grinds to a halt).

Using this system, we aim to investigate the evolutionary trajectories of P. aeruginosa when challenged with intense selection pressures e.g., in a polymicrobial environment, or upon exposure to antimicrobial agents or nutrient limitation. Project will involve elements of synthetic biology, microbiology, evolutionary biology, modelling and genomics. A stable polymicrobial culture system has recently been developed by the lab and is available for use.  

416
Category:
Microbiology and Infectious Disease
Project:

Mechanisms of dengue virus antigenic evolution

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
NIH Mentor:

Dr. Leah Katzelnick

University:
Cambridge
Project Details:

Dengue viruses continue to circulate endemically through large parts of the globe. Dengue virus is an antigenically variable pathogen, with individuals able to get reinfected numerous times. The risk of severe disease or death is increased in individuals with pre-existing antibodies generated from prior infections. This antibody-dependent phenomenon has complicated efforts to generate vaccines. The proposed research program aims to tackle this complexity through the combination of computational and experimental work in a joint project between the laboratories of Dr. Henrik Salje, a Professor at the University of Cambridge and the head of the Pathogen Dynamics Group and Dr. Leah Katzelnick, who is Chief of the Viral Epidemiology and Immunity Unit at the NIH. These two labs have a long track of working together, especially focusing research on well characterised settings where we have been able to characterise antigenic, genetic and epidemiologic features of dengue within the same communities. We have previously shown that there are long term trends in the antigenic properties of viruses circulating in the same location, suggesting of evolutionary pressures from local immunity. However, the exact immune and genetic mechanisms remain unknown.

In this PhD project, we will use computational approaches to identify candidate amino acid sites that are linked with shifts in antigenic space and to track these changes over a 30 year period. We will then experimentally test the antigenic movement of viruses mutated at the candidate locations. Finally, we will evaluate how antigenic shifts relate to dengue epidemic dynamics and disease. This project will provide much needed insight into how pathogens change to escape immunity, and will help guide vaccine efforts.

352
Category:
Microbiology and Infectious Disease
Project:

Investigating the impact of Trichuris trichiura infection during Inflammatory Bowel Disease (IBD) using organoids

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
NIH Mentor:

Dr. P'ng Loke

University:
Cambridge
Project Details:

Whipworms (Trichuris trichiura) are intestinal parasites that infect hundreds of millions of people worldwide and cause trichuriasis, a major Neglected Tropical Disease. Whipworms live preferentially in the caecum of their hosts and have a unique life cycle strategy where they establish a multi-intracellular niche within the intestinal epithelia (IE). In this niche, whipworms can remain for years causing chronic infections by modulating intestinal inflammation. During IBD the IE is damaged and recent findings identified a pivotal role of the IE in the maintenance of inflammation. IBD is rare in countries where trichuriasis is endemic, suggesting that the control of inflammation evolved by whipworms in order to persist in their epithelial niche during chronic infections may have beneficial effects for its host by limiting bystander inflammatory pathologies. Current IBD therapies using live parasitic worms, including whipworms (T. trichiura and T. suis), worm secretions and worm-derived synthetic molecules are being trialled to treat IBD.  However, the effects of whipworms on the IE during IBD are poorly understood. Intestinal organoids are in vitro multicellular clusters resulting from stem cell self-renewal and organization that closely recapitulate the composition and architecture of the IE. We have shown that murine caecal organoids (caecaloids) stimulated with extracellular vesicles purified from adult T. muris (mouse whipworm) excretory-secretory (ES) products show a downregulation of genes normally involved in virus responses, specifically type-1 interferon signalling. This data led us to hypothesise that the anti-inflammatory effects of whipworm infections as IBD therapy are partly mediated by direct effects on the IE.

For this PhD project, we will adapt our murine caecal organoid-whipworm model
 to human organoids and T. trichiura. We will generate intestinal organoids from biopsies of IBD patients, healthy controls and individuals experimentally infected with T. trichiura in human challenge infections. These studies will offer insights on the inflammatory and stem cell remodelling pathways modulated by whipworms in the IE and will lead to the dissection of the molecular mechanisms promoting whipworm persistence in the host but also with beneficial effects for therapies on IBD.

 

238
Category:
Microbiology and Infectious Disease
Project:

Transmission of bacteria and antimicrobial resistance determinants between and among animals and humans

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
University:
Cambridge
Project Details:

We are interested in the transmission of bacterial pathogens and AMR determinants at multiple scales from the within-hospital level to global networks. Projects are possible on many large-scale datasets, primarily using population genomic and phylogenetic approaches to investigate these processes.

213
Category:
Microbiology and Infectious Disease
Project:

Mechanisms underlying DNA replication and cell cycle control in Plasmodium

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
University:
Cambridge
Project Details:

My group studies the human malaria parasite Plasmodium falciparum.  Collaborative PhD projects can be offered in research areas centered around Plasmodium DNA biology: we are particularly interested in the molecular mechanisms underlying DNA replication and cell cycle control in Plasmodium, which replicates by an unusual method called schizogony.  We are also interested in mechanisms for silencing and promoting the recombination of a family of key virulence genes called var genes - particularly the role that G-quadruplex DNA structures may play in var gene control.  In fact, we have recently discovered that G-quadruplexes and their helicases have more general roles in genome stability and evolution in the malaria parasite as well.

211
Category:
Microbiology and Infectious Disease
Project:

Understanding genetic susceptibility to nontuberculous mycobacterial infections

Project Listed Date:
Institute or Center:
National Institute of Allergy and Infectious Diseases (NIAID)
NIH Mentor:

Dr. Steve Holland

University:
Cambridge
Project Details:

This collaborative project between Dr. Steven Holland’s laboratory at the NIH and Dr. Lalita Ramakrishnan’s lab at the University of Cambridge will seek to understand the mechanistic basis of human susceptibility to environmental mycobacteria that are nonpathogenic to most people but can cause serious disease in individuals with specific immune deficiencies. Dr. Holland runs an international referral service that takes care of a unique cohort of patients with genetic susceptibility to nontuberculous mycobacterial infections. In the lab, they are mapping these susceptibilities and have found then to map to distinct immune genes, e.g., IRF8 and GATA-2, myeloid growth factors, IL-12R, the GTPase Rac2, to name only a few. 

Dr. Ramakrishnan’s group has pioneered the optically transparent and genetically tractable zebrafish as a model for mycobacterial pathogenesis. The use of the zebrafish has enabled discoveries about TB immunopathogenesis and the genetic basis of susceptibility to TB which has led to the discovery of a variety of inexpensive, approved drugs that can be used to treat TB, often in a patient genotype-directed manner. They have also used the zebrafish to understand the mechanism of leprosy neuropathy.

Through this joint project, the two labs will work together to harness the power of the zebrafish to understand the molecular and cellular basis of the human susceptibilities identified by Holland. The student will move between humans and fish (and Bethesda and Cambridge) to uncover fundamental mechanisms of mycobacterial disease pathogenesis while acquiring mastery over the disciplines immunology, infectious diseases, genetics, molecular biology and cell biology.

210
Category:
Microbiology and Infectious Disease
Project:

Using genetic and cellular tools to identify and prioritise malaria vaccine targets

Project Listed Date:
Institute or Center:
N/A
NIH Mentor:
N/A
UK Mentor:

Prof. Julian Rayner

University:
Cambridge
Project Details:

There are more than 200 million clinical cases of malaria each year, leading to nearly half a million deaths, primarily among children in Africa. The two major tools for malaria control, antimalarial drugs and insecticides, are both seriously threatened by resistance, making the search for a highly effective malaria vaccine more urgent than ever. My lab focuses on the malaria parasite blood stages, during which parasites invade, multiply inside and consume human erythrocytes. The process of erythrocyte invasion represents a brief extracellular window in the parasite life cycle when parasites are exposed to the antibody-mediated immune system, making it a potential vaccine target. A number of vaccine-related projects are available that intersect with the interests of NIH collaborators in the NIAID Malaria Research Program, from systematic screening of new potential vaccine candidates, to deep structural understanding of current high-profile candidates, to understanding natural immunity to malaria by working with partners in endemic countries in order to inform better vaccine design. All could involve a mix of new technologies, including CRISPR/Cas9 engineering of parasite genomes, and represent an opportunity to contribute to the long-term battle against one of humanities oldest and most persistent infectious disease foes.

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