Phosphorylation is a vital regulatory mechanism in cells. Alterations in phosphorylation signalling are major contributors to disease, and numerous clinically important drugs target kinases to treat cancer and other diseases. Characterising signalling networks is therefore crucial for cell biology research, to understand changes in disease, to improve predictions of drug efficacy and patient response to targeted therapies, and to identify reliable biomarkers and molecular diagnostic tools. The UK-based company Kinomica, for example, offers mass-spectrometry-based and computational services to the biotech and pharma industry that interrogate thousands of phosphorylation sites and elucidate large cellular phosphoproteomic networks.
However, although thousands of cellular phosphorylation sites are known, identifying the kinases for particular phosphorylation events is a major roadblock. To address this problem, we recently developed a generally applicable method (“KiPIK”) that uses panels of chemical inhibitors to identify kinases for specific phosphorylation sites. The method has clear advantages over in silico and genetic screening, and it has potential to help reveal kinase pathway rewiring in development and diseases such as cancer, and to uncover the role of understudied “dark” kinases.
In this CASE studentship, you will work in a multidisciplinary team with the primary supervisor at Newcastle University and with Kinomica Ltd. You will use KiPIK to determine the kinases responsible for phosphorylation of substrates with related consensus sites in cell signalling pathways that are altered in diseases such as cancer (eg targets of basophilic kinases such as Akt), and address gaps in knowledge of kinase-substrate relationships identified using Kinomica’s phosphoproteome platform. You will gain knowledge and skills in cell and kinase biology, high-throughput screening/robotics, proteomics, quantitative analysis and integration of large datasets, and machine learning.
The project will elucidate new kinase signalling pathways, and validate the KiPIK method as a platform for fundamental and disease-based research. This information will also increase the value of Kinomica’s KScan technology platform for discovery science and precision medicine.
HOW TO APPLY
Applications should be made by emailing [Email Address Removed] with:
· a CV (including contact details of at least two academic (or other relevant) referees);
· a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;
· copies of your relevant undergraduate degree transcripts and certificates;
· a copy of your passport (photo page).
A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.
In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
Informal enquiries may be made to [Email Address Removed]. The closing date for applications is 10th January 2022 at 5.00pm (UK time).