PhD studentship - Defining the mechanisms underpinning HIF-1 and HIF-2 dependent transcriptional specificity in hypoxia

Award Summary

100% of home tuition fees paid and annual living expenses of £18,622 

Overview

The cellular response to low oxygen levels (hypoxia), is crucial for cell survival and identity. At the cellular level, the transcriptional response is primarily orchestrated by the transcription factor Hypoxia-Inducible Factor (HIF). In low oxygen conditions, HIF is rapidly stabilised, initiating transcription of genes involved in processes such as metabolism and angiogenesis, to restore oxygen balance and promote cell survival. Hypoxia and HIF activation underpin many diseases like cancer and neurodegeneration, emphasising the need to understand HIF's regulatory mechanisms. 

HIF is a heterodimeric transcription factor with oxygen-sensitive alpha subunits (HIF1-α and HIF-2α) and an oxygen-insensitive beta subunit (HIF1β). While HIF-1 and HIF-2 recognise identical genetic sequences and share common target genes, they also have distinct DNA-binding patterns and regulate unique cellular processes. However, the precise mechanisms governing their transcriptional specificity are unclear. One potential mechanism may involve interaction with specific chromatin-associated protein complexes. Unravelling how HIF-1 and HIF-2 exert their specific activities holds therapeutic potential, allowing selective modulation of HIF's functional arms to alter cell function and treat disease. 

This project will use genetic screening and proteomic techniques (RIME and proximity labelling) to identify factors conferring transcriptional specificity to HIF-1 and HIF-2 activity. The identified targets will undergo validation through biochemical assays and functional studies to elucidate their roles in regulating the activity of HIF-1 and HIF-2 in disease relevant models. 

Number Of Awards

1

Start Date

30th September 2024

Award Duration

3 years

Application Closing Date

1st April 2024

Sponsor

Newcastle University Academic Tract (NUAcT) Fellowship 

Supervisors

Dr Brian Ortmann and Professor Neil Perkins 

Eligibility Criteria

You must have, or be predicted, at least a 2:1 honours degree or have an MRes, in an appropriate subject, including: cell biology and genetics.  

This studentship is only available to applicants with a Home fee status (UK and EU applicants with pre-settled/settled status and meet the residency criteria). 

How To Apply

To apply for a studentship, you must register and apply through the University’s Apply to Newcastle Portal 

Once registered select ‘Create a Postgraduate Application’.  

Use ‘Course Search’ to identify your programme of study:  

• search for the ‘Course Title’ using the programme code: 8420F 
• Leave the ‘Research Area’ field blank  
• select ‘PhD Biosciences (FT)' as the programme of study 

You will need to provide the following information in the ‘Further Details’ section:  

• A ‘Personal Statement’ - upload a document or write a statement directly in to the application form  
• Studentship code BI084 in ‘Studentship/Partnership Reference’ field  
• When prompted for how you are providing your research proposal - select ‘Write Proposal’. You should then type in the title of the research project from this advert - you do not need to upload a research proposal. 

 In addition, before you submit your application you will need to upload the following supporting documentation:  

• covering letter and CV. The covering letter must state the title of the studentship, quote reference code BI084 and state how your interests and experience relate to the project   
• degree transcripts and certificates and, if English is not your first language, a copy of your English language qualification if already completed.  

Contact Details

For informal enquiries, please contact brian.ortmann@newcastle.ac.uk  

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