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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.

209 Search Results

466
Category:
Neuroscience
Project:

The role of spontaneous body movements for neural processing in the visual cortex in sighted and blind subjects: a cross-species comparison

Project Listed Date:
Institute or Center:
National Eye Institute (NEI)
UK Mentor:

Prof. Holly Bridge

University:
Oxford
Project Details:

The laboratory of Prof. Bridge in Oxford uses multi-modal MRI to understand the pathways in the human visual system, and how they are affected by vision loss early or late in life.

The laboratory of Dr. Nienborg at the NIH combines behavior, neurophysiology, and videography in mammalian animal models to better understand how the visual system processes information depending on the animal’s behavioral and cognitive state. 


Visual processing during natural behavior requires subjects to distinguish between changes in visual information caused by a subject’s own body movements (e.g. by walking along a street), and those caused by changes in the external world (e.g. a car driving by). How the brain achieves this is fundamental to understanding visual perception. Moreover, the degree to which their own body movements affect processing in visual cortex in normally sighted and blind subjects has direct implications for the development of neural prostheses targeting the visual cortex.

The project will have two objectives:

  1. Identify how spontaneous body movements affect processing in the visual cortex in a mammalian animal model during head-free, naturalistic behavior.
  2. Compare the modulations in the visual cortex by a subject’s own body movements in sighted and blind human participants.

This project will allow students to learn wireless electrophysiological recordings in mammalian animal models (e.g. non-human primates or a highly visual rodent species) combined with videography during naturalistic behavior. Students will also be able to learn how to leverage recent machine learning approaches for the analysis of the video and neural data. Additionally, students will have the opportunity to learn how to acquire and analyze functional MRI data in sighted and blind human subjects, using a variety of tools.  

465
Category:
Virology
Project:

Quantitative proteomic analysis of the host-pandemic virus interaction

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

Evolution has produced an arms race between viruses and the cells they infect. Studying this battle provides key insights into cell biology and immunology, as well as the viruses themselves. It may even lead to the development of novel therapeutics. The Matheson lab therefore focuses on two pandemic viruses with a major impact on human health: HIV and SARS-CoV-2.  

We have previously used unbiased proteomics to quantify dysregulation of hundreds of proteins and processes in infected cells, and now aim to understand the importance of these targets for both viral pathogenesis and normal cellular physiology. Because HIV regulates numerous cell surface amino acid transporters, we are particularly interested in amino acid metabolism and protein biosynthesis.  

Depending on the interests of the student, this project will therefore focus on either (1) an orphan cell surface amino transporter downregulated by SARS-CoV-2 infection of respiratory epithelial cells or (2) an ancient metabolic enzyme regulating ribosomal frame shifting depleted by HIV infection of primary human CD4+ T cells.  

In either case, the aims will be to: validate the target in different systems; define the mechanism of viral regulation; determine the functional effects of target depletion in biochemical and cell biological assays; and characterise the impact of target depletion on viral infection. Opportunities will be available to conduct further proteomic screens, perform ribosomal profiling and/or stable isotope-based metabolomics.   

The project will provide training in a wide range of molecular and biochemical techniques, whilst allowing the student to explore an important aspect of the host-virus interaction. The Matheson lab is based in the brand new Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), including the largest academic Containment Level 3 (CL3) facility in the UK. The student will be supervised by an experienced postdoc in a friendly, supportive group. 
 

464
Category:
Computational Biology
Project:

Computational modelling in large scale imaging datasets to understand hypertensive disease progression after pregnancy

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

Our research group aims to understand hypertensive disease progression of women and their children following pregnancy complications, such as hypertensive pregnancy and preterm birth, to identify optimal approaches to reduce long term risk. This includes development of new clinical tools to identify, track, and slow the disease progression as well as novel interventions.

This project will apply computational modelling and machine learning to large scale imaging datasets to study disease progression related to a hypertensive pregnancy across multiple modalities and organs. The insights into key structural and functional changes at the organ-level that describe stages of disease will be used to identify potential intervention targets.

Furthermore, we will use imaging data collected within our ongoing clinical trials to help us understand how interventions modify the underlying disease development and how this could be incorporated in clinical practice to transform long-term patient outcomes after a hypertensive pregnancy.

463
Category:
Social and Behavioral Sciences
Project:

Exploring health research study design and community-based research perceptions

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

Prof. Trudie Lang

University:
Oxford
Project Details:

Our group works to enable health research in diseases, communities and settings where evidence to enable prevention, treatment and management of devasting burdens to health are woefully lacking. Our research sets out to understand how research methods, processes, skills and implementation could happen better, and be locally-led, in the most underserved regions across the globe. Our approaches are typically participatory, mixed-methods action research. This could be exploring health research study design, or how to work with the community to tackle perceptions about research and how to overcome these.

We work with health research teams and health workers across Africa, Asia and Latin America and work together to look closely at the challenges they are experiencing in the design, set-up, operational delivery and reporting of their research. We seek to work with them to identify better methods and approaches. We work in delivering skills training and capacity development and we also use digital technology and want to use advances in machine learning to drive equity in access to knowledge so that researchers, wherever they are, have access to the same quality and volume of training and resources.

Undertaking a DPhil with us could involve clinical trial design, or the application of AI in healthcare. It could have a social science or health economic component. Our DPhil projects always involve working in partnership with our collaborators in the Global South, and therefore travel and capturing data in those settings would be very likely. All our research is about tackling the inequity about where health research happens, who leads and who benefits from the data.

462
Category:
Neuroscience
Project:

Developing new methodology to study layered connectivity in the human brain using MRI

Project Listed Date:
Institute or Center:
National Institute of Mental Health (NIMH)
UK Mentor:

Prof. Saad Jbabdi 

University:
Oxford
Project Details:

What sets the brain apart from other organs is its complex connectivity. In order to study brain function, we need techniques for measuring brain connections with high precision in living humans. The goal of this project is to develop new methods for measuring brain connections using magnetic resonance imaging (MRI).

The project focuses on the cortex, a thin sheet of grey matter surrounding the brain. The cortex is well developed in primates, particularly humans, and plays a key role in cognition. It has a characteristic layered structure; each layer containing different varieties of neurons and connections. The input and output of a cortical region is determined by the connections of the layers. Thus, measuring layer connectivity can give us key insight into information flow in the brain. But these detailed anatomical patterns have only been studied in animal brains, where it is possible to precisely delineate connections.

This project aims to develop new methodology to study layered connectivity in the human brain using MRI. The incredible flexibility of MRI allows us to sensitise the measured signals to multiple aspects of tissue microstructure. We will use this flexibility to create MRI measurements that are sensitive to cortical lamination and integrate these measurements with computational models of laminar connectivity.

This project will open the door to addressing new questions about human brain organisation, such as whether brain areas are organized hierarchically, how information flows across the brain during cognition, learning, and memory; and what happens in diseases that disrupt brain connections

461
Category:
Immunology
Project:

Investigating the impact of regulatory cell therapy on local immune response in kidney allografts

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

Dr. Joanna Hester

UK Mentor:
N/A
University:
Oxford
Project Details:

Regulatory T cells (Tregs) have the ability to suppress allogeneic immune responses and have therefore become interesting as a possible cellular therapy.  Our group is leading a phase II randomised clinical trial utilising Tregs as a cellular therapy for kidney transplant recipients.

The proposed project aims to in depth investigate the local immune response within the transplanted allograft, specifically focusing on infiltrating regulatory T cells and their local interactions with other infiltrating immune cells, utilising renal biopsy samples from the cell therapy trial.  We hypothesise, that cellular therapy with regulatory T cells will result in trafficking of the Tregs cells to the allograft and creation of a local tolerogenic microenvironment.

We are proposing to utilise our unique collection of Treg treated patients’ biopsy samples employing the cutting-edge technology of spatial transcriptomics and single cell RNA sequencing to determine the cellular and molecular composition of leukocyte infiltrates in allograft biopsies, dissect cellular interactions in situ and determine Treg homing to the allograft.

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.

 

459
Category:
Cancer Biology
Project:

Understanding the XPO7:SLK complex to formulate synergistic combination therapies

Project Listed Date:
Institute or Center:
National Cancer Institute (NCI)
UK Mentor:

Prof. Jon Elkins

University:
Oxford
Project Details:

Most translational efforts for uncommon cancers stem from oncogenic mutations identified by sequencing. In contrast to genomic analyses, the tumor proteome has the potential to better approximate phenotype-inducing alterations, particularly in the absence of targetable driver mutations. However, tumor analyses using mass spectrometry can be challenging. Exosomes (small extracellular membrane-enclosed vesicles) may circumvent these issues and serve as a valuable, prioritized, “window” into the tumor cell proteome. Applying this reasoning to bile duct cancers (cholangiocarcinoma, CCA), we performed mass spectrometry on exosomes extracted from patient bile, revealing a 17-fold enhancement of the nuclear export protein XPO7. Immunohistochemistry analysis of XPO7 expression in 318 CCA patients unexpectedly demonstrated intense cytoplasmic staining. Within the cytosol we demonstrate that XPO7 exists in a molecular complex with the serine/threonine kinase SLK. shRNA-mediated knockdown of either XPO7 or SLK in CCA lines abrogated tumor organoid formation and reduced orthotopic tumor growth. To translate the target to patients, we identified tivozanib as a potent SLK inhibitor. Tivozanib treatment reduced tumor organoid formation in vitro and induced tumor regression in vivo in patient derived xenografts (n=2). Together, these findings reveal a novel cytosolic XPO7:SLK signaling axis that is targetable in CCA patients and we have already documented early responses with our accruing Phase I/II trial (NCT 04645160). It is however clear that single agents will not result in cures for patients with solid tumors, and a better understanding of the XPO7:SLK complex (including downstream oncogenic signaling axes) will be required to formulate and implement synergistic combination therapies.

458
Category:
Genetics & Genomics
Project:

Exploring the role of an evolutionary conserved anti-inflammatory protein in Drosophila and mice

Project Listed Date:
Institute or Center:
National Institute of Environmental Health Sciences (NIEHS)
NIH Mentor:

Dr. Perry Blackshear

University:
Oxford
Project Details:

Persistent inflammation is a pathogenic determinant in many common human diseases, including rheumatoid arthritis, Crohn’s disease, multiple sclerosis, and psoriasis, while playing a key role in the development of type-2 diabetes, obesity, certain forms of cancer, and neurodegenerative conditions such as Parkinson’s and Alzheimer’s diseases. The laboratory of Dr. Blackshear has identified tristetraprolin (TTP) as a protein that acts to restrict inflammation in mice by destabilising the mRNA of pro-inflammatory cytokines such as TNF, GM-CSF, CXCL1 and CXCL2. Mice where an instability-conferring element within TTP’s own mRNA was deleted using homologous recombination were remarkably resistant to inflammatory disease. Most importantly, these mice did not exhibit any pathology, presumably because of the relatively modest over-expression of TTP that was otherwise subject to normal regulation.  

However, studies of TTP’s biochemical and molecular activities have been hampered by the existence of three other members of the same protein family in the mouse.  Each of these proteins exhibits similar biochemical activities in cell transfection experiments and in cell-free assays, but knockout mice of each have led to dramatically different phenotypes, involving early development, hematopoiesis, and placental function rather than inflammation.  For this reason, we will use the fruit-fly Drosophila melanogaster, which expresses only a single TTP family member, known as TIS11. Using genetics, biochemistry, transcriptomics, and proteomics we will explore the role of TIS11 and extrapolate findings to experiments in mammalian systems at NIEHS.

457
Category:
Molecular Pharmacology
Project:

Examining a new class of drugs named Sympathofacilitators

Project Listed Date:
Institute or Center:
National Cancer Institute (NCI)
NIH Mentor:

Dr. Barry O'Keefe

UK Mentor:

Prof. Ana Domingos

University:
Oxford
Project Details:

Sympathetic neurons have a wide range of physiological functions and their hypoactivity contributes to obesity and diabetes, among other syndromes. Sympathomimemic drugs rescue this deficiency but this drug class, mostly composed of brain-penetrant amphetamines and adrenergic agonist, is both cardiotoxic and highly controlled. Our recent publication puts forward new class of drugs named Sympathofacilitators that do not enter the brain and have an anti-obesity and cardio-neutral effect in vivo. The first in-class was published in Mahu I, Domingos, et al. Cell Metabolism 2020; Figure 3C of this paper demonstrated a neuro-facilitatory effect, rather than neuro-excitatory one.

This new class is in need of novel chemical entities which can be screened in vitro on cultured iPSC-derived sympathetic neurons. The screen would be based on fluorescent readouts of calcium activity reporter, screening for a facilitation of responses to acetylcholine (similar to Figure 3C of Mahu I, et al).

The prospect of identifying natural compounds that have a Sympathofacilitatory effect is tangible when performed in collaboration with the laboratory of Barry O'Keefe. The student will learn how to grow and scale-up iPSC-derived sympathetic neurons in the Domingos lab, and optimize an in vitro assay based on Figure 3C. The student will then transfer this knowledge to the lab of Barry O'Keefe where the screen will be performed using a fluorescent plate reader, robotic liquid handling, and a library of natural compounds.

456
Category:
Immunology
Project:

Examining the anatomical and molecular aspects of new gene involvement and the effects of antigen-specific therapy

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

Dr. Michael Lenardo 

University:
Oxford
Project Details:

Autoimmune central nervous system (CNS) demyelinating diseases, especially multiple sclerosis (MS) are a major public health burden and poorly controlled by current immunosuppressants. More precise immunotherapies with higher efficacy and fewer side effects are sought.

We are investigating genetic basis of autoimmunity genomic DNA sequencing of the largest cohort of MS patients and family members (14,000 specimens) in an effort to improve therapy. We are also evaluating the effectiveness and mechanism of an
injectable myelin-based antigenic polyprotein MMPt to achieve antigen-specific treatment of MS. We find that it suppresses mouse experimental autoimmune encephalomyelitis (EAE) without major side effects. MMPt induces rapid apoptosis of the encephalitogenic T cells and suppresses inflammation in the affected CNS. Intravital microscopy shows that MMPt is taken up by perivascular F4/80+ cells but not conventional antigen-presenting dendritic cells, B cells, or microglia. MMPt-stimulated F4/80+ cells induce reactive T-cell immobilization and apoptosis in situ, resulting in reduced infiltration of inflammatory cells and chemokine production.

Our study will examine the anatomical and molecular aspects of new gene involvement and the effects of antigen-specific therapy to reveal new mechanisms that explain how cognate antigen suppresses CNS inflammation and may be applicable for effectively and safely treating demyelinating diseases.

455
Category:
Computational Biology
Project:

Understanding the clonality of drug resistance in cancer

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

Prof. Adam Cribbs

University:
Oxford
Project Details:

We are interested in understanding the clonality of drug resistance in cancer (primarily in a haematological cancer called Multiple Myeloma (MM)). To achieve our goals, we have developed state of the art long-read single-cell sequencing approaches (termed scCOLOR-seq) that allow us to measure single clones within patient samples. This method allows for the simultaneous measurement of gene expression, exon mutations, exon SNPs and translocations. We apply this technology and develop cutting edge computational analysis solutions to understand the relationship between clonality and drug resistance in oncology. Furthermore, our lab is also working as part of the Human Cell Atlas (HCA) project and we have several international collaborations with immunologists, cancer biologists to support our work.

The aim of this project is to develop computational analysis strategies aimed at better defining specific MM clones within patients that are resistant to first line therapeutics. The work will involve combining long-read (Oxford Nanopore Technology) multi-modal datasets and performing machine learning approaches to better define high risk patients. This work is important to better understand drug resistance mechanisms in MM and identify patients that may respond less well to therapy.

454
Category:
Immunology
Project:

Immuno-parasitology and epidemiology of helminths and SARS-CoV-2 coinfections

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 poor understanding of the effects of co-infection with parasitic helminths on SARS-CoV-2 infection. National Institute of Allergy and Infectious Disease (NIAID) and University of Oxford researchers are collaborating to study the effects of helminth co-infection on the immunological and patient-centered clinical outcomes of SARS-CoV-2 infection in India. In addition to deep immunological and microbiome profiling, they will investigate relevant comorbidities and socioecological confounders, as well conduct detailed epidemiological analyses of (co)infection risk factors, clinical/medical care outcomes. The project intends to discern whether SARS-CoV-2 infection is more or less likely among individuals with helminth infections when compared to individuals without helminth coinfections and to determine whether SARS-CoV-2 coinfection with helminths can cause antagonistic or synergistic long-lasting clinical outcomes, as well as detailed immune-phenotypes of infected individuals. Field studies will be conducted in the Tiruvallur District of Tamil Nadu, India by a NIAID-Indian Council on Medical Research (ICMR) International Center for Excellence in Research team based in Chennai.

This project is an exciting opportunity to combine work in immunology with epidemiology. You will join multidisciplinary labs at the NIH and Oxford

453
Category:
Project:

Investigating mechanisms of ER-associated degradation (ERAD) in human disease

Project Listed Date:
Institute or Center:
National Cancer Institute (NCI)
NIH Mentor:

Dr. Susan Lea

University:
Oxford
Project Details:

Accumulation of misfolded proteins and aberrant protein aggregates are hallmarks of a wide range of pathologies such as neurodegenerative diseases and cancer. Under normal conditions, these potentially toxic protein species are kept at low levels due to a variety of quality control mechanisms that detect and selectively promote their degradation. Our lab investigates these protein quality control processes with a particular focus on ER-associated degradation (ERAD), that looks after membrane and secreted proteins. The ERAD pathway is evolutionarily conserved and in mammals, targets thousands of proteins influencing a wide range of cellular processes, from lipid homeostasis and stress responses to cell signaling and communication.

We investigate the mechanisms of ERAD using multidisciplinary approaches both in human and yeast cells. Using CRISPR-based genome-wide genetic screens and light microscopy experiments we identify and characterize molecular components involved in the degradation of disease-relevant toxic proteins. In parallel, we use biochemical tools to dissect mechanistically the various steps of the ERAD pathways. In this collaborative project with the Lea lab we will use structural approaches such as cryo-electron microscopy to gain insight into the molecular mechanisms of ERAD.

These studies, by providing mechanistic understanding of the ERAD process, may shed light on human diseases impacting ER function and may ultimately contribute to better therapeutics. 

452
Category:
Neuroscience
Project:

Combining neuroimaging and neurophysiology to understand the nature of residual vision across species following damage to primary visual cortex

Project Listed Date:
Institute or Center:
National Institute of Mental Health (NIMH)
NIH Mentor:

Dr. David Leopold

UK Mentor:

Prof. Holly Bridge

University:
Oxford
Project Details:

The laboratory of Prof Bridge in Oxford focusses on understanding the pathways in the human visual system that can process residual vision after someone has had a stroke that affects the primary visual cortex.

The laboratory of Prof Leopold combines neuroimaging, behaviour and neurophysiology in a non-human primate model to better understand computation in the visual system, particularly relating to conscious perception.

The proposed PhD project would have 3 main objectives:

  1. Quantitatively compare changes in retinotopic maps and population receptive fields in humans and non-human primates with damage to primary visual cortex.
  2. Determine the visual pathways in the two species that are necessary and/or sufficient to provide residual vision within the blind region of the visual field.
  3. Investigate the neural changes that occur as a result of visual training following the damage to the visual system in order to inform rehabilitation programmes for people who have suffered a stroke to the visual system.

    During the training programme, the student would have the opportunity to learn about multi-modal human neuroimaging approaches applied to both the healthy and the damaged visual system. This would be complemented by training in both neuroimaging and neurophysiology in the non-human primate.
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