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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.

13 Search Results

229
Category:
Cell Biology
Project:

Develop and apply new super-resolution fluorescence and electron microscopy methods to the study of membrane traffic

Project Listed Date:
Institute or Center:
National Heart, Lung, and Blood Institute (NHLBI)
NIH Mentor:

Dr. Justin Taraska

UK Mentor:

Prof. Sean Munro

University:
Cambridge
Project Details:
N/A
216
Category:
Cell Biology
Project:

Function of specific VSMC-derived cell populations in human disease

Project Listed Date:
Institute or Center:
National Institute of Neurological Disorders and Stroke (NINDS)
NIH Mentor:

Dr. Carsten Bonnemann

University:
Cambridge
Project Details:

Accumulation of vascular smooth muscle cells (VSMCs) is a hallmark of cardiovascular diseases such as atherosclerosis, which cause heart attack and stroke. In healthy vessels, VSMC contraction regulate blood flow and blood pressure. In response to injury and inflammation, however, the cells lose their contractile function and undergo extensive transformation. This process results in the generation of a wide spectrum of phenotypically changed cells within atherosclerotic lesions, which are predicted to impact differently on disease progression. Using clonal lineage tracing in mouse models of atherosclerosis, we demonstrated that disease-associated cell accumulation result from extensive proliferation of a small subset of VSMC that can generate the full range of distinct cells. By combining lineage tracing with single cell RNA sequencing (sc-RNAseq) in mouse models, we have identified signatures of VSMC-derived cells subpopulations. Interestingly, cells displaying mesenchymal stem cell character are rare in healthy vessels and their numbers increase in disease models. The aim of this project is to study the function of specific VSMC-derived cell populations in human disease using a combination of genomics and functional assays. This work is important for efficient cell targeting in atherosclerotic lesions.

203
Category:
Cell Biology
Project:

Computational investigation of ligand-binding with a particular emphasis on membrane proteins

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

Prof. Philip Biggin

University:
Oxford
Project Details:
N/A
202
Category:
Cell Biology
Project:

Understanding how membrane-bound organelles form and acquire their distinctive proteome

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

My lab is interested in understanding how membrane-bound organelles form and acquire their distinctive proteome essential to carry their specialized functions. In particular, we focus on how organelle function is maintained through quality control processes, such as protein degradation. We are also interested in inter-organelle communications- which and how molecules are exchanged between organelles, which signals regulate those exchanges, etc.  Although my lab does mostly basic research, we are interested how these processes are disrupted in human disease.

181
Category:
Cell Biology
Project:

Mechanisms controlling organelle dynamics and quality control

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

Prof. Pedro Carvalho

University:
Oxford
Project Details:

Our lab is interested in membrane-bound organelles- how they form and acquire their distinctive proteome essential to carry their specialized functions. In particular, we focus on how organelle function is maintained through quality control processes. Our lab has been particular interested in a quality control process termed ERAD, which targets misfolded membrane proteins in the endoplasmic reticulum (ER). While some of the components of this process have been identified, the mechanisms by which diverse range of misfolded proteins are selected, ubiquitinated, extracted from the ER membrane and targeted for degradation by the proteasome remain elusive. To gain insight on the mechanisms of protein quality control our lab is taking multidisciplinary approaches. We are using CRISPR-based genome-wide genetic screens to delineate the molecular pathways involved in the degradation of disease-relevant misfolded proteins. In parallel, we use biochemical, proteomics and structural approaches to dissect mechanistically the multiple steps of ERAD. These studies will reveal the molecular basis of quality control processes by which misfolded and aggregation-prone proteins are handled by the cell both under normal and pathological situations. We are also interested in inter-organelle communications- which and how molecules are exchanged between organelles, which signals regulate those exchanges, etc.  Although we do mostly basic research, we are interested how these processes are disrupted in human disease.

157
Category:
Cell Biology
Project:

The tubulin code in health and disease

Project Listed Date:
Institute or Center:
National Institute of Neurological Disorders and Stroke (NINDS)
University:
Oxford
Project Details:
N/A
131
Category:
Cell Biology
Project:

Examining calcium and phospholipid signaling pathways

Project Listed Date:
Institute or Center:
National Institute of Child Health and Human Development (NICHD)
NIH Mentor:

Dr. Tamas Balla

UK Mentor:

Prof. Colin Taylor

University:
Cambridge
Project Details:

Close contacts between different membranes are important points of communication between intracellular membranes and between them and the plasma membrane. This project will use high-resolution optical microscopy and novel genetically encoded probes to examine the contribution of these membrane contact sites to spatially organized calcium and phospholipid signalling pathways.

102
Category:
Cell Biology
Project:

Myosin characterization using light microscopy

Project Listed Date:
Institute or Center:
National Heart, Lung, and Blood Institute (NHLBI)
NIH Mentor:

Dr. James Sellers

University:
Oxford
Project Details:

This project would be to extend a long standing and productive collaboration between the Kukura lab at Oxford and the Sellers lab at NIH.  The specialty of the Kukura lab is in the development of light microscopic approaches to study novel biological processes with high temporal and spatial resolution.  The strength of the Sellers lab is in the production and characterization of myosins using various biochemical and biophysical approaches.

101
Category:
Cell Biology
Project:

Molecular organization of axons and dendrites

Project Listed Date:
Institute or Center:
National Heart, Lung, and Blood Institute (NHLBI)
NIH Mentor:

Dr. Naoko Mizuno

UK Mentor:

Prof. Andrew Carter

University:
Cambridge
Project Details:

Neurons are specially shaped cells that have an extremely polarized structure. They contain protrusions called dendrites and a long axon extending from cell body that connect to neighbouring cells forming a neural network. Axons and dendrites retain a dynamic plasticity throughout the whole lifespan of a neuron to ensure the ability to adjust and adapt neural network connections.  The polarity and plasticity of neurons is maintained by a cytoskeleton of actin filaments and microtubules together with associated motors and other essential proteins.

 

This PhD project aims to elucidate the molecular organization of axons and dendrites using in situ cryo-electron tomography (cryo-ET) of primary neurons.  We will address how cytoskeletal filaments and motors drive the branching, elongation and neural network formation. To this end we form a strong collaboration between the lab of Andrew Carter at the Laboratory of Molecular Biology (LMB), Cambridge University and Mizuno Naoko at the National Heart, Lung and Blood Institute at NIH. Mizuno’s lab’s expertise is visualizing cell shape formations controlled by remodelling of cytoskeleton and the Carter lab has a long-standing interest in how trafficking is carried out by cytoskeletal motors.

 

Cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) bridge the resolution gap between light-microscopy and conventional structural methods for gaining information on a molecular level (X-ray crystallography/NMR).  Current technical developments further facilitate in-depth analysis of cells on a molecular level that has not been possible before. The skillset obtained in this PhD project will be highly relevant to the field of newly emerging structural cell biology.

100
Category:
Cell Biology
Project:

Crosstalk of the cell-surface membrane system

Project Listed Date:
Institute or Center:
National Heart, Lung, and Blood Institute (NHLBI)
NIH Mentor:

Dr. Naoko Mizuno

UK Mentor:

Prof. Yvonne Jones

University:
Oxford
Project Details:

The formation of neural network is essential for building a nerve system and to maintain its dynamic function. Neuronal cells extend their axons to connect to dendrites of partner neurons. The process is facilitated by axonal migration and controlled by the balance of the search for partner neurons vs the locking of axon-dendrite connections. This balance is maintained by two signaling pathways relying on the integrin receptor (mode of neurite migration) and the semaphorin receptor (mode of axon-dendrite locking). The inter-regulation between both pathways is mediated by the intracellular signaling factor Rap1. However, the mechanism of this interconnection is unknown.

 

This PhD project aims to elucidate the nature of this crosstalk using a bottom-up reconstitution of integrin, semaphorin and Rap1 by developing a cell-surface mimicking membrane system. We aim to establish a functional membrane system that allows us to control the two modes, i.e. attachment/detachment of two neighboring membranes representing dendrite and axon connections. The uniqueness of the project lies in the exact control of communication through membranes by the bottom-up strategy, which would be otherwise extremely challenging to elucidate. Moreover, the system will allow us to probe receptor interactions using biophysical, light microscopic as well as cryo-EM methods to understand the underlying principles of neural network formation and neuronal regeneration.

 

Our collaborative team has expertise in a wide variety of interdisciplinary techniques to facilitate the proposed PhD research, such as X-ray crystallography, cryo-EM, biophysical analysis, membrane biology and light microscopy. Mizuno lab is leading in the use of cryo-EM in combination with cellular methods to visualize cell shape formations controlled by the integrin signaling pathway and the remodeling of cytoskeleton components. Jones lab has a long-standing interest in axon guidance and structural biology of membrane proteins. Yvonne Jones co-heads the Structural Biology Division of the Wellcome Centre for Human Genetics at the University of Oxford.

 

This project will give a candidate a tremendous opportunity to apply cutting-edge in vitro reconstitution methods in the field of structural- and neuro- biology.

99
Category:
Cell Biology
Project:

Mitochondrial regulations and their roles in metabolic adaptation in hibernation

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

Dr. Wei Li

UK Mentor:

Dr. Mike Murphy

University:
Cambridge
Project Details:
N/A
98
Category:
Cell Biology
Project:

Developing Treatment Paradigms for Age-Related Macular Degeneration.

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

Dr. Kapil Bharti

UK Mentor:

Prof. Colin Goding

University:
Oxford
Project Details:

Age-related macular degeneration (AMD) is one of the leading causes of blindness among the elderly affecting over 30 million individuals world-wide. AMD initiates in the back of the eye because of dysfunctions in the retinal pigment epithelium (RPE), a monolayer of cells that maintains vision through maintenance of photoreceptor healthy and integrity. AMD can lead to severe vision loss and blindness in advanced stages – “dry” and “wet” forms. In the dry stage, the death of RPE cells triggers photoreceptor cell death and atrophy of the choroidal blood supply causing vision loss. It is thought that RPE cell death in AMD is triggered by the formation of sub-RPE protein/lipid deposits called drusen. Our recent work shows that drusen formation is initiated by reduced autophagic flux in RPE cells resulting in reduced ability of RPE cells to process intracellular “debris” that eventually gets secreted as drusen deposits. TFEB, a member of MiT family of transcription factors is a known master regulator of autophagy. Here, we propose to investigate the activity of transcription factor TEFB in our AMD cellular models of iPSC-derived RPE cells. We hypothesize that autophagy downregulation is triggered by post-translational changes in TFEB that affect its sub-cellular localization and reduce its transcriptional activity. Here, we propose to identify those changes in TEFB and discover signaling pathways that lead to its altered activity. Lastly, we will test the ability of our recently discovered FDA-approved drugs that stimulate TEFB activity to reduce drusen formation by increasing autophagy in iPSC-RPE AMD models. This work will lead to a better understanding of AMD pathogenesis and potentially retool existing  drugs to treat AMD patients.

90
Category:
Cell Biology
Project:

Chemical biology tools to study crosstalk between cell metabolism and protein degradation

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

Dr. Jordan Meier

UK Mentor:

Prof. Kilian Huber

University:
Oxford
Project Details:

In order to maintain homeostasis in response to environmental changes such as nutrient availability, eukaryotic cells have evolved intricate mechanisms to quickly increase or decrease the activity of fundamental processes such as gene expression, protein expression and degradation. Indeed, several metabolites act as cofactors for important cellular enzymes that regulate e.g. chromatin state and serve as templates for posttranslational modifications flagging proteins for proteolysis via the ubiquitin-proteasome system. Consequently, the identification of metabolites and complementary binding domains has broadened our understanding of human physiology and contributed to the development of new medicines to treat malignant and inflammatory disease. The aim of this project is to systematically map protein-metabolite interactions on a proteome-wide scale by combining the development of specific metabolite-inspired affinity reagents with unbiased approaches such as thermal profiling to dissect metabolite signalling in the context of protein degradation pathways in various cell types. Applicants will have the opportunity to take advantage of a unique combination of synthetic organic chemistry and cell biology techniques to identify new potential drug targets and develop first-in-class ligands for key regulators of protein homeostasis.

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