Dr Elena Bichenkova, Prof Aline Miller, Prof Alberto Saiani
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
This collaborative, multidisciplinary project is focused on the design and fabrication of novel DNA-based nano-biosensors using self-assembling peptidyl-oligonucleotide conjugates for the detection of (i) genetic abnormalities (at DNA level) as well as (ii) gene-expression profiling (at mRNA level) for potential application in molecular diagnostics and biomedicine.
Identification of genetic abnormalities that induce profound alterations of cellular functions, and thus cause monogenic or complex diseases (e.g. diabetes, rheumatoid arthritis, Alzheimer’s disease, cancer, and Parkinson’s disease) could be crucial in recognising patient susceptibility to certain disease states and in predicting adverse drug responses at earlier stages of therapeutic treatment. Rapid detection of RNA-based biomarkers offers the advantage of early diagnosis and treatment of various cancers. Thus, nano-technological approaches for fast, robust and reliable screening for such disease states may facilitate effective therapeutic interventions with fewer side effects, which will undoubtedly lead to improved health and quality of life for the benefit of UK healthcare and society.
The aim of this project is to develop a new generation of nano-biosensors for detection of disease-relevant biomarkers based on self-assembling peptidyl-oligonucleotide hydrogels by chemical conjugation, where the oligonucleotide component will serve as recognition motif to ‘fish out’ and sense certain DNA or mRNA sequences from biological samples thus allowing signal generation and detection. The controlled assembly of individual molecules into desired nano-architectures will be precisely engineered by manipulating the chemical structure of the nano-molecular building blocks to trigger fluorescence signal on binding with disease-relevant DNA or RNA molecules.
The training will be provided at the interfaces between structural biology, chemistry, biophysics and molecular modelling. The recruited PhD student will benefit from established collaborations to develop research expertise across chemical biology, high-level molecular simulation and modelling, structural biophysics, drug delivery and translational medicine. This will encourage the recruited student to appreciate and value collaborative and coordinated multidisciplinary approaches necessary to resolve healthcare grand challenges. Given the breadth of biophysical science, computational and pharmaceutical chemistry skills provided, such training would support progression into a variety of career positions within academic or industrial settings involving pharmaceutical sciences, medicinal chemistry, nanoscience or biotechnology. Graduates with skills-sets spanning these areas are rare, so the training would provide a solid platform for career development.
Applicants should hold (or expect to obtain) a minimum upper-second honours degree (or equivalent) in chemistry, biochemistry, biophysics or relevant physical sciences subject with previous experience in analytical and spectroscopic techniques. They must also be capable of working at the interface between chemistry, biology and nanotechnology. Some experience in material sciences would be highly beneficial. A Masters qualification in a similar area would be a significant advantage.
Funding Notes
This project has a Band 2 fee. Details of our different fee bands can be found on our website (https://www.bmh.manchester.ac.uk/study/research/fees/). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor.
References
1. Bichenkova E.V. , Lang Z., Yu X., Rogert C., Douglas K.T. ‘DNA-mounted self-assembly: New approaches for genomic analysis and SNP detection’. Biochim. Biophys. Acta. Gene Regulatory Mechanisms (2011), Volume 1809 (Issue 1), 1-23.
2. G. Ribas, A. Gonz´alez-Neira, A. Salas, R.L. Milne, A. Vega, et al, Evaluating HapMap SNP data transferability in a large-scale genotyping project involving 175 cancer-associated genes. Hum. Genet. 118, (2006) 669–679.
3. A. Tahiri, S.K. Leivonsen, T. Lüders, I. Steinfeld, M. Ragle Aure, J. Geisler, R. Mäkelä, S. Nord, M.L. Riis, Z. Yakhini, K. Kleivi Sahlberg, A.L. Børresen-Dale,M. Perälä, I.R. Bukholm, V.N. Kristensen. Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumour’. Carcinogenesis, 2014, 35, 76-85.
4. K. Ono, Y. Kuwabara, J. Han. ‘MicroRNAs and cardiovascular diseases’ FEBS (2011), 278, 1619-1633.
5. King P.J., Saiani A., Bichenkova E.V., Miller A.F. ‘A de novo self-assembling peptide hydrogel biosensor with covalently immobilised DNA-recognising motifs’. Chem Commun (2016) 52, 6697-6700.