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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.

12 Search Results

243
Category:
Genetics & Genomics
Project:

Using population genomic approaches to evaluate Anopheles gambiae

Project Listed Date:
Institute or Center:
National Human Genome Research Institute (NHGRI)
NIH Mentor:

Dr. Adam Phillippy

University:
Cambridge
Project Details:

Population genomic approaches across diverse species have traditionally used short read sequence data to investigate population structure and signatures of selection. In the recent past, long reads are more traditionally used to build reference genomes to which the short read data can be aligned and evaluated. However, the cost of long read sequencing as well as the DNA input required to generate high quality long read data is dropping rapidly. We foresee a future where population genomics transitions to long read data.

 

Using these emerging technologies, this project will begin to evaluate what new insights are gained for the Anopheles gambiae species complex, a set of mosquito species famous as the vector of malaria and known to exhibit porous species boundaries and abundant structural variation.  We anticipate that long-read approaches for haplotype phasing and structural variant discovery will enable much clearer resolution of gene flow within species, introgression between species, and alleles under directional or balancing selection.  Insights gained from this project are likely to influence approaches taken for other species that are known to have similar complexities (e.g., Heliconius butterflies, African cichlid fishes).

 

This project will involve developing and applying new computational methods for analysing long-read sequencing data in an Anopheles population genomics context. The collaborating laboratories at the Sanger Institute and NHGRI are experts in these respective areas and well-suited to provide the appropriate mentorship.

194
Category:
Genetics & Genomics
Project:

Genomic and genetic basis of sex differences in development, physiology, and behavior

Project Listed Date:
Institute or Center:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIH Mentor:

Dr. Ben Oliver

UK Mentor:

Prof. Stephen Goodwin (Oxford) &
Prof. Steve Russell (Cambridge)
 

University:
N/A
Project Details:
N/A
183
Category:
Genetics & Genomics
Project:

Analyses of paired host-virus genomic data to understand disease heterogeneity of viral infections

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

Genome-wide association studies (GWAS) aim to identify the genetic basis of phenotypic traits using the variation that exists within natural populations. Uniquely for infectious diseases, the inter-individual heterogeneity in disease phenotype is linked to both host and pathogen genetic variation. Traditionally, genetic studies of infectious diseases have sought to explain between-individual variation in disease phenotypes by assessing genetic factors separately in humans or pathogens, under the assumption that these factors are independent. Although reasonable for some variants, there is strong theoretical and empirical evidence that genetic interactions between host and viruses play a major role in viral disease aetiology.

 

In this project you will integrate host and viral genomic data from the same patients to better understand viral pathogenesis and between-individual heterogeneity in disease outcomes. By analysis of paired host-virus genomic data from well-characterised cohorts you will gain novel insights on (a) host polymorphisms linked with viral sequence variation, (b) virus sites under strong host genetic selective pressures, (c) host and virus genetic factors independently contributing to disease phenotypes and (d) host-virus genetic interactions contributing to disease phenotypes. The findings have the potential to: (I) revolutionize our understanding of host-virus interactions and human biology; (II) aid in development of more effective vaccines, drug targets and immunotherapies; and (III) permit better use of therapies through patient stratification. In the age of “Big Data” and “Personalised Medicine”, analysis of paired host-pathogen genomic data will become increasingly important to uncover the mechanisms driving pathogen adaptations and heterogeneity of infection outcomes.

178
Category:
Genetics & Genomics
Project:

Examining inhibitors of DNA repair as cancer therapy

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

Prof. Nick Lakin

University:
Oxford
Project Details:

Inhibitors of DNA repair have emerged as powerful agents in cancer therapy, either as monotherapies that exploit synthetic lethal interactions between DNA repair pathways, or by increasing the efficacy of chemo- and radiotherapies. Principal in this strategy is inhibition of Poly(ADP-ribose)-polymerases (PARPs), enzymes that regulate DNA strand break repair, and PARP inhibitors (PARPi) are being used to treat tumours with defects in homologous recombination (HR). However, this strategy is restricted to treating ovarian cancers, with limited information on why PARPi are toxic to HR-defective cells, or additional synthetic lethal interactions that will broaden their application to treat other tumours.

By combining our expertise in PARP biology and DNA repair (e.g. Ronson, et al. Nat Commun 9: 746) with cutting edge genome editing, proteomics and cell biology, this project will address this fundamentally important question by characterising novel cancer-related genes that are synthetic lethal with PARP dysfunction. Through a genome-wide CRISPR-Cas9 screen, we identified a novel gene (PASL9) that is synthetic lethal with PARPi. Our data indicate PASL9 is critical to resolve replication-associated DNA damage through a mechanism that is mutated in colorectal cancers. Through multidisciplinary hypothesis-driven research, this research will: a) Define the nature of synthetic lethality between PARPs and PASL9; b) Establish the repair mechanism regulated by PASL9; c) Assess PASL9 as a target to treat colorectal cancer. These studies will define the mechanistic basis of how PARPs and PASL9 maintain genome stability and define novel strategies to exploit PARPi to treat a variety of tumours.

173
Category:
Genetics & Genomics
Project:

Examining the physical, functional and genetic relationship between DNA helicase BLM and the mammalian DNA mismatch repair system

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

Dr. Andre Nussenzweig

University:
Oxford
Project Details:

DNA mismatch repair is a system cells use to recognize and repair mis-incorporated DNA bases that can arise during DNA replication and recombination. Loss of mismatch repair activity causes a form of DNA hypermutability called microsatellite instability, and predisposes to colorectal, endometrial and other cancers. Recently, it was found that inhibition of the RecQ DNA helicase WRN specifically kills cancer cells with microsatellite instability1, thus providing an attractive drug target to treat cancers with defects in DNA mismatch repair. Unfortunately, small molecule inhibitors targeting WRN do not yet exist, but inhibitors that target the closed related RecQ DNA helicase BLM have already been developed. However, is still unclear whether and how BLM interacts with the DNA mismatch repair pathway.

 

The aim of this project will be to examine the physical, functional and genetic relationship between BLM and the mammalian DNA mismatch repair system in human cells as well as in mouse models. The student will have the opportunity to gain experience in super-resolution microscopy, CRISPR-Cas9 gene-editing, next-generation sequencing methods (including END-seq and GLOE-seq), mouse models and high-throughput screening for drug discovery, in addition to standard molecular and cell biology techniques.

171
Category:
Genetics & Genomics
Project:

Role of extracellular vesicle miRNAs in preeclampsia

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

Prof. Manu Vatish 

University:
Oxford
Project Details:

Preeclampsia is a multi-system hypertensive disorder of pregnancy that is caused by placental dysfunction.  The placenta releases extracellular vesicles (EVs) into the maternal circulation from early pregnancy all the way to term as part of its normal function. These EVs have proteins on the surface and contain genetic cargo, capable of altering maternal cellular function. It is known that the release, protein and genetic content of EVs is altered in preeclampsia. We have optimised an ex-vivo placental perfusion technique that permits isolation of trophoblast EVs. We have isolated EVs from normal and preeclampsia subjected these to proteomic and sequencing analysis. It is apparent that there are significant differences in miRNA and other non-coding RNA between EVs from normal and PE placentae. These differences have been validated by RT-PCR. We now wish to investigate the downstream cellular effects of the miRNAs/non-coding sequences, in cell models (endothelial, hepatic etc.) using transfected HEK293 cells. KEK293 cells constitutively produce exosomes. The transfected HEK293 cell will produce exosomes enriched for the RNA species of interest and allow specific miRNA effects to be determined using deep sequencing and proteomics analyses of the target cell. Analysis will require the candidate to be trained in bioinformatics approaches.

Simultaneously, we will interrogate a cohort of clinical samples for circulating miRNAs and investigate their role as a potential biomarker of placental function/disease. The NDWRH sits within the Women’s Centre at the John Radcliffe hospital and delivers 8000 women per year. 

169
Category:
Genetics & Genomics
Project:

Maintenance of genome stability through histone ADP-ribosylation

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

Maintaining genome integrity through DNA repair is critical for human health and defects in these pathways result in cancer, neurodegeneration and premature ageing. Understanding DNA repair mechanisms will provide insights into the underlying causes of these conditions and strategies for their treatment. For example, inhibitors of Poly(ADP-ribose) polymerases (PARPs), enzymes that regulate DNA strand break repair, are used to treat DNA repair deficient tumours, with the potential to treat other malignancies.

 

However, despite the use of PARP inhibitors in the clinic, the substrates modified by these enzymes and how they regulate DNA repair are ill-defined. For example, although histones are targets for ADP-ribosylation (ADPr) following DNA damage, how this regulates genome stability either directly, or through competition with other histone post-translational modifications (PTMs) is unclear.  This, in part, is due to the absence of an experimental platform in which PARPs and histone ADPr sites can be manipulated in tandem. These criteria are met in the eukaryotic model organism Dictyostelium and we have identified histone ADPr sites modified in response to DNA damage in this organism. We will exploit the unique ability to introduce site-specific ADPr mutations into endogenous Dictyostelium histone genes to define how ADPr regulates DNA repair either directly, or through influencing other histone PTMs. We will identify novel proteins that specifically interact with ADPr histones and characterise these factors in human cells. Together, this work will uncover how cells maintain genome integrity that will inform novel strategies to refine the use of PARP inhibitors in the clinic.

144
Category:
Genetics & Genomics
Project:

Genomic and genetic basis of sex differences in development, physiology, and behavior.

Project Listed Date:
Institute or Center:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIH Mentor:

Dr. Brian Oliver

UK Mentor:
N/A
University:
N/A
Project Details:
N/A
139
Category:
Genetics & Genomics
Project:

Understanding how germ cells ensure genome integrity and the survival of future generations

Project Listed Date:
Institute or Center:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIH Mentor:

Dr. Astrid Haase

University:
Cambridge
Project Details:

Germline genomes are immortal.  Their genetic information is transmitted to the next generation and ensures that continuation of life.  To protect the integrity of their genomic information, germ cells employ a specialized small RNA-based defense system, PIWI-interacting small RNAs (piRNAs) and their PIWI protein partners.  The interest of the Karam Teixera lab in germ cell biology and evolution and the focus of the Haase lab on mechanisms of small silencing RNAs converge on piRNA-guided surveillance of genome integrity. The collaborative project of an OxCam Scholar is designed to combine strength of both labs in genetics, biochemistry and genomics, and offers training in experimental techniques and basic computational analyses of next-generation sequencing data.  Results from this graduate study will further our understanding of how germ cells ensure genome integrity and the survival of future generations. 

118
Category:
Genetics & Genomics
Project:

How do disease-inducing mutations affect inflammasome formation and activation?

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

Prof. Clare Bryant

University:
Cambridge
Project Details:
N/A
110
Category:
Genetics & Genomics
Project:

Interplays between genome, the epigenome and the environment in shaping the development of brain and behavior.

Project Listed Date:
Institute or Center:
National Human Genome Research Institute (NHGRI)
NIH Mentor:

Dr. Philip Shaw

UK Mentor:
N/A
University:
N/A
Project Details:
N/A
103
Category:
Genetics & Genomics
Project:

Association between age-associated DNA mutations and atherosclerotic disease risk

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

Dr. Chris Hourigan 

UK Mentor:

Prof. Chris O'Callaghan

University:
Oxford
Project Details:

It is well recognized that acquired genetic mutations are an important cause of cancer, but recent studies have suggested that such somatic mutations are also associated with atherosclerosis. Somatic mutations have been found in blood from 10% of people over 70 years of age and 20% of people over 90 years of age and appear associated with an increased risk of atherosclerotic disease. Although age is a known independent risk factor for atherosclerosis, the basis for this has not been known.  It now appears likely that these mutations, several of which are found in genes known to regulate inflammation and immunity, are either a direct contributor to, or a potential biomarker for, this age-associated risk. The challenge now is to identify molecular mechanisms linking these somatic mutations with atherosclerosis.

 

This PhD project will investigate the cellular and molecular basis of the association between age associated DNA mutations and atherosclerotic disease risk. To do this will require cross-disciplinary collaboration, so this project brings together two highly complementary groups to address this important new biomedical challenge. At the National Heart, Lung and Blood Institute of the NIH, Chris Hourigan works on these acquired mutations in the context of a blood cancer called acute myeloid leukemia. At Oxford, Chris O’Callaghan works on molecular mechanisms involved in atherosclerosis and the genetic control of those mechanisms, especially in vessel wall inflammation.

 

This is a very exciting new field and has potential to identify new drug targets and so benefit patients with atherosclerosis. The experience gained by this doctorate will be highly relevant to other fields and will include cellular and molecular biology, high throughput sequencing approaches including single cell approaches and analysis of genetic variation.

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