header-bg

Research Opportunities

Background Header
Image
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.

8 Search Results

420
Category:
Stem Cell Biology
Project:

Disease pacemaker Stem Cells in Neurodegenerative Disease

Project Listed Date:
Institute or Center:
National Institute on Aging (NIA)
NIH Mentor:

Dr. Isabel Beerman

University:
Cambridge
Project Details:

The presence and role of neural stem cells (NSCs) in the adult human brain is a long-debated issue in neuroscience. Recent work has demonstrated that stem-like cells exist in the embryonic, foetal, and human adult brain where they persist well into adulthood and can even contribute to neurogenesis. However, their role in neurodegenerative disease is unknown. Ongoing work in the lab has led to the hypothesis that NSCs may become dysfunctional in neurodegenerative disease resulting in senescence chronic inflammation, and thereby acting as pacemaker cells driving neuronal demise. This ambitious project aims to identify disease-associated NSCs and their phenotype in the context of human neurodegeneration using spatial biology approaches, including imaging mass cytometry, RNA scope and single nuclear RNA sequencing. Relying on post-mortem brain tissue of different stages of Alzheimer’s disease, traumatic brain injury, vascular dementia and chronic stroke, this project will study NSCs in a range of human diseases characterised by neurodegeneration and neuronal injury. Ongoing work in the lab identifies NSC-specific markers based on transcriptomics and protein profiling experiments in brains with progressive multiple sclerosis, enabling to investigate the distribution of NSCs in a wide range of diseases. Spatial transcriptomics and proteomic approaches will allow to study their phenotype and dysfunction in relation to other cell types and local pathology. This project will shed light on the role of NSCs in neurodegeneration and has the potential to identify an entirely novel mechanism of neurodegeneration in human disease.

This project will be co-supervised by Prof. A. Quaegebeur.

419
Category:
Stem Cell Biology
Project:

Investigating the molecular regulation of hematopoietic stem cell fitness

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

Dr. Stefan Muljo

University:
Oxford
Project Details:

Multipotent self-renewing hematopoietic stem cells (HSCs) support life-long blood system homeostasis and play essential roles in human disease and its therapy. HSC transplantation is an important cell therapy for a range of hematological diseases including immunodeficiencies, beta-globinopathies, and blood cancers. Through their ability for self-renewal and multipotency, HSCs can reconstitute the hematopoietic system following transplantation. Most HSC transplants are performed using allogeneic HSCs but there is also a growing interest in the development and use of autologous HSC transplantation gene therapies for a range of non-malignant blood diseases. A major unresolved question in the field is what regulates the fitness of an HSC. High fitness HSCs display durable and balanced blood system reconstitution activities. By contrast, low fitness HSCs have weak or biased activities. The accumulation of low fitness HSCs is thought to contribute to various disease pathologies and their use in HSC transplantation can result in engraftment failure. Building on research interests in the Muljo lab at the NIH and the Wilkinson lab at the University of Oxford, this project will focus on characterizing transcriptional and post-transcriptional mechanisms regulating HSC fitness. Biological mechanisms identified here will be used to devise new strategies to enhance life-long hematopoietic system health and to improve the safety and efficacy of HSC transplantation therapies.
 

Recent publications:

Wang, S., Chim, B., Su, Y., Khil, P., Wong, M., Wang, X., Foroushani, A., Smith, P. T., Liu, X., Li, R., Ganesan, S., Kanellopoulou, C., Hafner, M. and S. A. Muljo. Enhancement of LIN28B-induced hematopoietic reprogramming by IGF2BP3. Genes & Development, 33: 1048–1068. DOI: 10.1101/gad.325100.119.

Wilkinson, A.C., Ishida, R., Kikuchi, M., Sudo, K., Morita, M., Crisostomo, R.V., Yamamoto, R., Loh, K.M., Nakamura, Y., Watanabe, M., Nakauchi, H. and S. Yamazaki. (2019). Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation. Nature, 571: 117–121. DOI: 10.1038/s41586-019-1244-x.

Haney, M.S., Shankar, A., Hsu, I., Miyauchi, M., Palovics, R., Khoo, H.M., Igarashi, K.J., Bhadury, J., Munson, C., Mack, P.K., Tan, T., Wyss-Coray, T., Nakauchi, H., Wilkinson, A.C. Large-scale in vivo CRISPR screens identify SAGA complex members as a key regulators of HSC lineage commitment and aging. bioRxiv 2022. DOI: 10.1101/2022.07.22.501030

417
Category:
Stem Cell Biology
Project:

Developmental timing in mammalian stem cell models

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

Prof. Teresa Rayon

University:
Cambridge
Project Details:

The Rayon’s lab (www.rayonlab.org) overall aim at the Babraham Institute in Cambridge is to investigate the molecular and metabolic pathways that control biological timing and lifespan. To answer these questions, we work with mouse and human stem cells and embryos and employ a variety of quantitative and genomic techniques. We are looking for applicants that are curious about evolution, developmental biology and embryonic stem cells.

We are interested in the following topics:

  1.  Exploring the role of cell numbers and cell cycle length in developmental timing in mammals. We plan to study differentiation in the absence of cell cycle and to establish mouse and human co-cultures.
  2.  Understanding the regulation of enhancer timing. We want to test the existence of species-specific enhancers and their dynamics.
  3.  To develop a high-content imaging assay to screen for modulators of timing. Develop a screen to explore if epigenetic, metabolic, and turnover factors impact the pace of differentiation.

A background on cell culture or molecular biology, as well as skills in bioinformatics or computational approaches would be useful, but ample opportunities for training will be provided.

415
Category:
Stem Cell Biology
Project:

Antiviral mechanisms in Brain Stem Cells in Development and Cancer

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

Virus infection of brain stem cells represents a major global health concern, but also offers treatment possibilities in neurodegenerative diseases and in malignant brain tumours. For example, Zika Virus targets SOX2+ neural progenitors in the developing brain to cause microcephaly in babies born to mothers infected during pregnancy; likewise, it targets SOX2+ glioma stem cells in the most common and lethal malignant brain tumour, glioblastoma (GBM) (https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4135719). Stem cells have been shown to exploit a distinct set of antiviral mechanisms compared to somatic cells (https://doi.org/10.1016/j.cell.2017.11.018), and viral permissivity varies widely between example developing brain and glioblastoma stem cell populations. Understanding and manipulating the cell-intrinsic mechanisms underpinning antiviral resistance in brain stem cells will inform approaches to protect and exploit neural stem cell function and to ablate cancer stem cells in GBM.

This project will seek to understand and modify viral permissivity and antiviral defence mechanisms in developing brain and brain tumours, focusing on stem cell intrinsic pathways. In the first place we will  address the hypothesis that immune selection pressure on glioma stem cells during tumour development results in expansion of a mesenchymal/injury-response cell population (https://www.cell.com/cell/pdf/S0092-8674(21)00351-2.pdf) refractory to virus infection, then proceed to examine underlying mechanisms.

You will be working with human patient-derived and mouse defined mutation glioma cell models, treated with viruses and viral mimetic compounds. You will be assaying transcriptional identity and responses using qPCR and RNA sequencing, immunofluorescence and RNA smFISH, and cytokine secretion using immunoassays. The lab has access to the state-of-the-art Cambridge Stem Cell Institute imaging, FACS, sequencing and bioinformatic facilities, and to additional specialist facilities (e.g. imaging mass cytometry) in the CRUK Cancer Institute next door. We will validate results in mice in vivo and/or slice cultures prepared from  human developing brain and patient brain tumour tissue, models we have established and use routinely in the lab.

395
Category:
Stem Cell Biology
Project:

Elucidating the role of disease modifying gene variants in inherited cardiomyopathies using induced pluripotent stem cell derived cardiomyocytes and CRISPR/Cas-9

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

Our group is interested in uncovering and understanding key mechanisms of disease that affect cardiac muscle function. We have a particular interest in understanding how regulation of cardiac muscle contraction is altered in common acquired and inherited cardiovascular diseases. We do this by using cutting edge techniques in cellular imaging, employing human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs), and CRISPR/Cas-9 to understand human cardiovascular disease in the dish.
 

We have two key focuses in the lab:

  1. Understanding how inherited heart conditions including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) alter cardiomyocyte function. We do this by using CRISPR Cas-9 genome engineering in combination with iPSC-CMs to screen how HCM and DCM causing variants cause disease. We can then use these systems to screen novel therapeutics in the dish. We have designed multiple techniques to make these analyses feasible and rapidly deployable: SarcTrack and CalTrack.
     
  2.  Investigate the processes that alter cardiac muscle function in acquired cardiac diseases including myocardial infarction, atrial fibrillation, and heart failure. We are able to use biochemical techniques twinned with fluorescent imaging to assess how cardiac myosin states are altered in disease tissues. This technology allows us to uncover key disease mechanisms that alter heart muscle function, allowing insight into these common heart muscle diseases. 
     

We have multiple key collaborations within the University of Oxford and internationally. Together we focus on pushing the boundaries of understanding in acquired and inherited cardiovascular disorders of the heart muscle. Within the group we have an inclusive and diverse set of researchers who have a wide range of cutting-edge expertise. Within the wider lab environment and our collaboration network we have over 20 researchers in this area.
 

Scientific training opportunities in the lab include but are not limited to:
 

  1. Induced pluripotent stem cell culture
  2. Techniques for iPSC to cardiomyocyte differentiation
  3. CRISPR/Cas-9 genome engineering
  4. PCR and genetic sequencing
  5. A wide range of standard fluorescent microscopy and confocal microscopy
  6. Phenotyping of cardiomyocyte function with fluorescent probes and genetically encoded protein tags
  7. RNA sequencing and qPCR
  8. Western blotting and phosphoprotein blotting techniques
  9. Drug screening using live cell microscopy

Transferrable skills include but are not limited to:
 

  1. Learning to interact with MatLab and other computing packages for automating and simplifying data analysis.
  2. Using genome viewers and associated software for designing and executing CRISPR/Cas-9 engineering.

References:

  1.  Hypertrophic cardiomyopathy mutations in MYBPC3 dysregulate myosin Science Translational Medicine 2019
  2. Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy Circulation 2020
  3. SarcTrack An Adaptable Software Tool for Efficient Large-Scale Analysis of Sarcomere Function in hiPSC-Cardiomyocytes Circulation Research 2019
  4. CalTrack: High-Throughput Automated Calcium Transient Analysis in Cardiomyocytes Circulation Research 2021
  5. Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity Nature Genetics 2021
147
Category:
Stem Cell Biology
Project:

Identifying genes involved in stem cell fate specification

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

Dr. Guang Hu

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

Pluripotent stem cells, such as embryonic stem cells (ESCs), can be used as a model system to study the molecular basis of fate-specification during early mammalian development. They can also be used to derive various types of cells for disease modeling, drug discovery, regenerative medicine, and environmental health sciences. To fully realize these potentials of pluripotent stem cells, it is important to understand the molecular mechanisms that regulate the pluripotent state. We have previously carried out a genome-wide RNAi screen in mouse ESCs and identified a list of novel factors that are important for pluripotency maintenance. Among them, we are currently investigating the function of the Ccr4-Not mRNA deadenylase complex and the INO80 chromatin remodeling complex in ESCs, somatic cell reprogramming, and mouse development using biochemical, genetic, genomic and single cell analysis approaches. In addition, we are developing new genetic and genomic methods to identify and probe genes involved in stem cell fate specification. We are applying these methods in pluripotent and germline stem cells to better understand the maintenance, transition, resolution, and re-establishment of the pluripotent state.

113
Category:
Stem Cell Biology
Project:

Elucidating fetal haematopoiesis in mouse and human

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

Dr. Stefan Muljo

UK Mentor:

Prof. Anindita Roy

University:
Oxford
Project Details:

Hematopoiesis is a finely tuned process by which mature blood cells of multiple lineages are constantly generated throughout life from hematopoietic stem cells. In humans, definitive hematopoiesis commences in the fetal liver (FL) at around five weeks of gestation, and remains the main site of hematopoiesis throughout fetal life. Hematopoiesis in the bone marrow (BM) starts around 11-12 weeks of gestation, but does not take over as the primary site of hematopoiesis until just after birth. Recent evidence suggests that fetal hematopoiesis is distinct from postnatal hematopoiesis in many ways. Most of these studies have been done on mouse models, but whether these differences exist in, or are a true reflection of hematopoiesis in the human setting, remains to be determined. We, and others have begun to investigate unique features of human fetal hematopoiesis and this project will determine fetal specific programmes that change through ontogeny. This may depend on the physiological processes or demands of that particular developmental stage, and/or in response to specific microenvironmental cues. This research is clinically relevant since the transplantation of hematopoietic stem cells from donors of different ages vary in their regenerative and differentiation potential. Studying hematopoiesis throughout the human lifespan may be important not only to understand normal developmental processes, but also to understand the pathogenesis of postnatal haematological diseases that may have their origins in fetal life. Research by the Roy laboratory particularly focuses on properties of fetal cells that contribute to leukemia initiation in utero and how these might change after birth, and we have recently developed a unique infant acute lymphocytic leukemia (ALL) model. We are particularly interested in ‘oncofetal’ genes that might define the biology of infant and childhood leukemias; and whether they can be manipulated for therapeutic interventions.

*This project is available for the 2021 Oxford-NIH Pilot Programme*

97
Category:
Stem Cell Biology
Project:

Translation research on degenerative eye diseases using induced pluripotent stem cells.

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

Dr. Kapil Bharti

UK Mentor:
N/A
University:
N/A
Project Details:
N/A
Back to Top