Learning from and outperforming nature: Computationally reconstructing and experimentally screening ancestral proteins to understand the evolution of signaling systems at University of Cambridge on FindAPhD.com

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Cambridge United Kingdom Biochemistry Cancer Biology Evolution Machine Learning Chemistry

About the Project

This is a unique opportunity for PhD study in the world-leading Cancer Research UK Cambridge Institute (CRUK CI) to start a research career in an environment committed to training outstanding cancer research scientists of the future. The Institute has excellent state-of-the-art facilities and research ranges from basic biology and computational biology through to translational cancer research and clinical application.

Graduate students play a pivotal role in the continuing success of our research programmes. If you are interested in contributing to our success, please find further information at: https://www.cruk.cam.ac.uk/jobs-and-studentships/postgraduate-study

Dr Pau Creixell wishes to recruit a student to work on the project entitled: Learning from and outperforming nature: Computationally reconstructing and experimentally screening ancestral proteins to understand the evolution of signaling systems

For further information about the research group, including their most recent publications, please visit their website:

https://www.creixell-lab.com

Project description:

Our lab integrates machine learning and high-throughput biochemistry to study how proteins selectively recognise their substrates, how this process is perturbed in cancer and how it can be hijacked to find highly selective and mutant-specific drugs to overcome drug resistance.

In our lab we are resolving how and when signaling systems evolved using in silico reconstruction and high-throughput biochemical characterization of ancestral proteins, the main goal of this project. Since some of the signaling systems that we study have emerged multiple times, our lab is in a unique position to address a fundamental question in protein biochemistry and evolution; whether the evolution of a new molecular function is dictated by biophysical constraints, contingent on a particular evolutionary history, or just one of many possibilities that could have arisen. In addressing these questions, we will also be able to analyze and quantify the degree to which we can engineer synthetic proteins whose function supersedes the ones from extant and ancestral natural ones.

Qualifications/Skills:

As a relatively new lab, we are particularly interested in students who will be highly motivated and share our excitement for science. You should be independent while also capable of taking feedback and input from others. While we will consider candidates from all backgrounds, those with interests in biology and biochemistry, chemistry, physics and/or machine learning/artificial intelligence may have an advantage.

Funding:

Please indicate that you wish to be considered for funding by answering ‘Yes – I wish to apply for funding’ on your application form. By ticking ‘yes’ you will be considered for a number of funds, including a Cancer Research UK studentship that includes full funding for University and College fees and in addition, a stipend currently of £21,000 per annum, initially for 3 years, with funding for a further year as required.

How to apply:

Please apply using the University Applicant Portal. For further information about the course and to access the applicant portal, go to:

https://www.postgraduate.study.cam.ac.uk/courses/directory/cvcrpdmsc

Please select to commence study in Michaelmas term 2024 (October 2024).

To complete your on-line application, you need to provide the following:

Reference Request: The names and contact details of two academic referees who have agreed to act on your behalf.

Course Specific Question: Your statement of interest (limit of 2,500 characters) should explain why you wish to be considered for the studentship and which qualities and experience you will bring to the role. Please also state how you learned of the studentship.

Supporting Document: Please upload your CV (PDF file), which should include a list of the examinations taken at undergraduate level and if possible, your examination results

Deadline:

The closing date for applications is 13 November 2023 with interviews expected to take place in the week beginning 15 January 2024.

Funding Notes

No nationality restrictions apply to Cancer Research UK funded studentships. Applications are invited from recent graduates or final year undergraduates who hold or expect to gain a first/upper second-class degree (or equivalent) in a relevant subject from any recognised university worldwide. Applicants with relevant research experience, gained through Master’s study or while working in a laboratory, are strongly encouraged to apply.

References

Martyn, G.D. & Veggiani, G. Cold Spring Harb. Protoc. (2023) doi: 10.1101/pdb.over107981
Park, Y. et al. Science 376, 823-830 (2022).
Xie, V.C. et al. eLife 10, 1-34 (2021).
Georg K. A. Hochberg, G.K.A., et al. Nature 588, 503-508 (2020).
Hochberg, G. K. A. & Thornton, J. W. Annu Rev Biophys 46, 247–269 (2017).
Thornton, J. W. Nat Rev Genet 5, 366–375 (2004).
Shah, N. H. et al. Elife (2016). doi:10.7554/elife.20105
Glass, D.S. & Riedel-Kruse, I.H. Cell 174, 649–658 (2018).
Mou, Y. et al. JACS 140, 16615–16624 (2018).
Begley, M. et al. Nat. Struct. & Mol. Bio 22(12), 983–990 (2015).