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  Synthetic Biology of the peroxisome


   Faculty of Biological Sciences

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Prof A Baker Dr Stuart Warriner  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

Compartmentalisation is a fundamental feature of eukaryotic cells and increases efficiency and complexity by segregating incompatible reactions and concentrating intermediates. Our previous work has utlised understanding of a key protein-protein interaction between a targeting signal and receptor to produce an ‘orthogonal pair;’ which can be used to deliver user specified protein components to the peroxisome. Use of a cell compartment for synthesis of high value biochemical or storage of high value proteins can potentially have deleterious effects due to negative impacts on essential endogenous processes and reactions, therefore this project seeks to build on our previous work to try to produce a completely orthogonal peroxisome that can co-exist with the native peroxisome in S.cerevisiae and thereby circumvent this problem. The project will combine cell biology and metabolic engineering type approaches to test our understanding of the rules for making and programming the metabolism of an organelle.

Funding Notes

White Rose BBSRC Doctoral Training Partnership in Mechanistic Biology
4 year fully-funded programme of integrated research and skills training, starting Oct 2020:
• Research Council Stipend
• UK/EU Tuition Fees
• Conference and research funding

Requirements:
At least a 2:1 honours degree or equivalent. We welcome students with backgrounds in biological, chemical or physical sciences, or mathematical backgrounds with an interest in biological questions.

EU candidates require 3 years of UK residency to receive full studentship

Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive process.

https://phd.leeds.ac.uk/funding/81-white-rose-bbsrc-doctoral-training-partnership-in-mechanistic-biology

References

Cross LL. Paudyal R. Kamisugi Y. Berry A .Cuming AC. Baker A. Warriner SL (2017) Towards designer organelles by subverting the peroxisomal import pathway. Nature Communications 8:454 (http://rdcu.be/vCkL )

DELOACHE, W. C., RUSS, Z. N. & DUEBER, J. E. 2016. Towards repurposing the yeast peroxisome for compartmentalizing heterologous metabolic pathways. Nature Communications, 7, 11152.

ZHOU, Y. J., BUIJS, N. A., ZHU, Z., GÓMEZ, D. O., BOONSOMBUTI, A., SIEWERS, V. & NIELSEN, J. 2016. Harnessing Yeast Peroxisomes for Biosynthesis of Fatty-Acid-Derived Biofuels and Chemicals with Relieved Side-Pathway Competition. Journal of the American Chemical Society, 138, 15368.


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Project supervisors

Career overview

Professor Alison Baker obtained a BA in Natural Sciences (Part II Biochemistry) from Cambridge University between 1979 and 1982. She then pursued a PhD at the University of Edinburgh in the Department of Botany from 1982 to 1985, focusing on nuclear genes encoding the ATP/ADP translocator of maize mitochondria under the supervision of Prof. CJ Leaver FRS. Following her doctoral studies, she undertook postdoctoral work at the Biozentrum, University of Basel from 1985 to 1988, where she researched protein import into yeast mitochondria under the supervision of Prof. G. Schatz, supported by an EMBO Fellowship from 1985 to 1987. From 1989 to 1995, Professor Baker served as an Assistant Lecturer and then as a Lecturer in the Department of Biochemistry at the University of Cambridge. In 1995, she joined the University of Leeds, where she has held various positions: Lecturer from 1995 to 1999, Senior Lecturer from 1999 to 2004, Reader in Plant Cell and Molecular Biology from 2004 to 2008, and has been a Professor of Plant Cell and Molecular Biology since 2008. Her research interests encompass a range of topics, including the use of photosynthetic aquatic organisms for nutrient recovery from wastewaters, enhancing phosphate use efficiency in millets, regulation of catalase targeting in plant cells, and the structure-function of the peroxisomal ABC transporter COMATOSE. The overarching theme of her work is the transport of molecules across biological membranes. Professor Baker collaborates with colleagues in various interdisciplinary projects, contributing to advancements in sustainability and nutrient recovery in agricultural practices.


Research interests

Professor Baker''s research focuses on the transport of molecules across biological membranes, with specific interests in four project areas. The first area involves the use of photosynthetic aquatic organisms for nutrient recovery from wastewaters, aiming to enhance the sustainability of nutrient recycling processes. This includes collaborations with colleagues in Civil Engineering and highlights such as uncoupling growth and phosphorus uptake in duckweed and manipulating growth conditions in microalgae to increase phosphorus uptake rates. The second area is enhancing phosphate use efficiency in millets, where Professor Baker collaborates with the International Crops Research Institute for the Semi-Arid Tropics and Rajagiri College in India. This research aims to develop crop plants with improved phosphorus use efficiency to reduce reliance on energy-intensive fertilisers. The third area of interest is the regulation of catalase targeting in plant cells, exploring how catalase, an important antioxidant enzyme, is targeted and functions in response to redox signalling. Recent findings include the presence of catalase in the nucleus of Arabidopsis. Lastly, Professor Baker investigates the structure-function relationship of the peroxisomal ABC transporter COMATOSE, which is involved in the import of substrates for beta-oxidation in peroxisomes. Current work focuses on determining the structure of this transporter and its substrate specificity. Overall, Professor Baker''s research integrates various aspects of plant cell and molecular biology, particularly concerning nutrient recovery, crop sustainability, and enzyme regulation.

View Professor Alison Baker's profile 
Career overview

Dr Stuart Warriner is a Senior Lecturer in the School of Chemistry at the University of Leeds. He has expertise in chemical biology, synthesis, and mass spectrometry. Dr Warriner serves as the Deputy Head of School and Admissions Tutor. His research group focuses on various aspects of chemical biology, including the investigation and manipulation of peroxisomal protein trafficking pathways in collaboration with Prof. Alison Baker. This research aims to enhance the understanding of the import process using chemical tools and to develop biotechnological applications. Additionally, Dr Warriner''s group is involved in discovering bioactive molecules and has developed the Activity Directed Synthesis platform in collaboration with Prof. Adam Nelson. His work extensively utilises mass spectrometry across various group projects and external collaborations. Dr Warriner welcomes enquiries from motivated and qualified applicants interested in pursuing PhD studies in his research areas.


Research interests

Dr Warriner''s research focuses on chemical biology, particularly in the area of peroxisomal protein trafficking pathways. He collaborates extensively with Prof. Alison Baker to enhance the understanding of the import process using chemical tools and to manipulate the peroxisomal import machinery for biotechnological applications. Additionally, Dr Warriner is interested in developing new strategies for the discovery of bioactive molecules, working alongside Prof. Adam Nelson on the Activity Directed Synthesis platform. His expertise in mass spectrometry is applied in various group projects and external collaborations, facilitating the analysis and characterisation of chemical compounds in his research.

View Dr Stuart Warriner's profile