DNA

HEATHER JEFFERY

HEATHER JEFFERY

BIOCHEMIST

About me Research Publications Industry Other Contact
About me Research Publications Industry Other Contact

ABOUT ME

I am doing a DPhil in Interdisciplinary Bioscience at the University of Oxford. I am researching chromatin accessibility around DNA replication origins in Saccharomyces cerevisiae with supervision by Conrad Nieduszynski, Nicholas Proudfoot and David Sims. Previously I studied Biochemistry with a Year in Research at Imperial College London.

Picture of Heather

CURRENT RESEARCH

Experimental and computational approaches to biological problems

Yeast cell cycle

Many cell functions rely on proteins, including transcription and replication factors, accessing DNA binding sites. The majority of DNA-binding proteins display preference for particular sequence motifs, though current chromatin structure experiments on populations of cells show vast variation. Studies have identified many "fuzzy" binding sites where the position differs between cells. It is not known if these are important for genome organisation or other protein binding in proximal sites.

This BBSRC-funded project seeks to develop a method that can be applied to single molecules to examine the true binding positions in individual cases, allowing potential interactions to be examined.

PAST RESEARCH

Sanger Sequencing

Primary lymphoedema

St George's University

Identification and analysis of genetic mutations from a subset of primary lymphoedema patients, with functional studies in human cells.

Cardiac arrhythmia

Cardiac arrhythmia

St George's University

Investigation of the effect of cardiac arrhythmia mutations in zebrafish. Funded by a Genetic Society Summer Studentship.

Transcription-cofactor interaction

Transcription-cofactor interaction

Imperial College London

In silico simulation, using molecular dynamics, of a transcription factor-coactivator complex found in humans with subsequent analysis of protein contacts.

Leishmania

Leishmania flagellar proteome

Oxford University

Identification of the functional effect of Leishmania mexicana flagellar proteins by CRISPR-Cas9 knockout and subsequent motility analysis and electron and fluorescence microscopy.

PUBLICATION HIGHLIGHTS

Leishmania: What’s in their tail?

Leishmania with fluorescently labelled flagella

Leishmania mexicana is a parasite that causes cutaneous leishmaniasis, a skin infection that is transmitted by sandflies. As a result, it is particularly prevalent in the tropics, subtropics and southern Europe. It is one of the less studied parasites despite affecting around one million people every year.

This study identified proteins that located to the tail (otherwise known as a flagella). Subsequently, one-hundred knock-out cell lines were produced, each of which was missing a single gene encoding a flagellar protein. Then their swimming ability was tested. Fifty-two mutant Leishmania swam slower and four swam faster while the rest maintained their normal swimming speed. Some were accompanied by a loss of co-ordination. A combination of fluorescence microscopy and electron microscopy enabled the identification of some structural differences in the flagella that may have caused the difference in motility.

A reduction in the ability to swim may prevent the Leishmania from reaching the midgut of the sandflies who transmit them between people. This work contributes to the understanding of fundamental Leishmania biology which in the future may lead to a reduction of leishmaniasis cases.

View the paper

What causes limbs to swell?

EPHB4 western blot

Primary lymphoedema is a group of disorders that are predominantly associated with swelling of a limb. This is caused by a build-up of fluid and is due to a problem with the lymphatic system. This system is important for immunity and for transporting lymph (similar to the liquid component of blood) from the tissues to the blood.

In recent years, the identification of additional symptoms has led to the development of a classification system for primary lymphoedema. This divides primary lymphoedema into a variety of syndromes, each of which have a unique combination of symptoms and a distinct genetic basis. One of these syndromes, lymphatic-related (non-immune) hydrops fetalis (LRHF) is a general swelling of the fetus, which can be fatal.

In this paper, the role of mutations in the gene for EPHB4, a protein involved in signalling processes during development was investigated. Biochemical analysis showed that specific mutations of EPHB4 in patients prevented phosphorylation (chemical modification) at these sites, which in turn prevented EPHB4 from passing the signal on. Without the phosphorylated sites, the signalling pathway is broken and development of the lymphatic system cannot proceed as normal. Furthermore, complete removal of the gene for EPHB4 has been linked to faulty lymphatic valve development. Therefore, the valves can no longer ensure the lymph flows one-way round the lymphatic system. This highlights the importance of EPHB4 in the early developmental stages of the lymphatic system.

The lymphatic system has many beneficial roles but in primary lymphoedema it can be a source of problems. Learning about the effect of mutations associated with primary lymphoedema is vital for informing future development of therapies.

View the paper

INDUSTRY EXPERIENCE

I was a research intern with Singer Instruments from December 2018 to March 2019. Here, I worked with both the research and software teams to test and develop lab automation robots.

Singer Instruments logo

OTHER ACTIVITIES

Entrepeneurship

Participation in the YES (Young Entrepeneurs Scheme) Biotechnology competition and a 4-day business course run by the MPLS division of the University of Oxford at Begbroke Science Park.

YES competition

Outreach

Design and implementation of activities for genetics-themed outreach activities for a range of ages. Events involve working with University departments, museums and schools.

Outreach

Teaching

University of Oxford

Demonstrator for an undergraduate 'Bacteriology' module and graduate 'Programming' and 'Bioinformatics' modules.

Writing

Involvement with the Sir William Dunn School of Pathology newsdesk, which involves writing both news articles and summaries of recent scientific publications by departmental scientists.

Beyond science

I am also a DipABRSM violinist with the Ozymandias String Quartet who regularly put on concerts and play for events. Additionally, I enjoy drawing.

Artwork

Contact


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