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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.

4 Search Results

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
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