Jordan Fletcher

Principal Scientist at Rosa Biotech
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Location
Bristol, England, United Kingdom, UK

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Experience

    • United Kingdom
    • Research Services
    • 1 - 100 Employee
    • Principal Scientist
      • Jul 2019 - Present
    • United Kingdom
    • Higher Education
    • 700 & Above Employee
    • Senior Research Associate
      • 2009 - 2019

      Research Associate: A Biomolecular-design Approach to Synthetic Biology with Prof. Dek Woolfson (The University of Bristol, UK). In this project we took a synthetic biology approach towards the design of a de novo synthetic cytoskeleton. First, we designed, synthesised, and characterised several coiled coils (a common protein fold in which two or more α-helices self-associate about a central hydrophobic core) of varying architecture producing a “basis set” for general applications in Synthetic Biology. Next, I took two of these coiled-coils and linked them together to give two complementary hubs with 3-fold symmetry. When mixed in solution they self-associate to give a 2D network of tessellated hexagons, which then curves and closes to form ~100 nm cage. This work culminated in a first-author publication in Science, and the successful filing of a patent to protect the work which was then leveraged for the successful application for multiple research grants. In January 2018 I begun work on a new project for the sensing of small molecules and complex mixtures. At the heart of this technology lays an array of higher order coiled coils which possess barrel-like architectures -- a property that can be readily exploited. To do so, we employ an environmentally sensitivity dye, which fluoresces when bound within the lumen of the barrels and can be competitively displaced. Interestingly, the extent of dye displacement varies between each barrel, thus enabling us to discriminate between various analytes. We have recently taken a mixed selection of barrel-forming peptides developed in-house, arrayed them, and measured dye-displacement for particular analytes. This produces characteristic fingerprints for given samples which can be used to train machine-learning techniques to identify patterns and to predict the molecules or mixtures that give rise to them. All told, this provides a unique method for analysis akin to a “chemical nose”. Show less

    • Australia
    • Higher Education
    • 700 & Above Employee
    • Research Fellow
      • 2007 - 2008

      Research Fellow: Development of T-cell Epitopes for the Treatment of Cancer with Prof. Mibel Aguilar & Prof. Patrick Perlmutter (Monash University, Australia) At Monash University I was focused on developing small, antigenic peptides with improved pharmacokinetics for the treatment of cancer. This was an industry-funded project and a collaboration between ourselves (at Monash University) and a team of immunologists based at the Bio21 institute (part of The University of Melbourne). In short, we took a number of known antigenic peptides which we modified at the backbone amide, effectively “scanning” with β-amino acids and N-methylation at each position. This yielded a number of hits – i.e. peptides possessing a vastly improved pharmacokinetic profile without any concomitant loss of efficacy versus that of the parent. Further, we were able to obtain X-ray crystal structures of our modified peptides bound to MHC and identify how our modifications were accommodated. Unfortunately, due to the nature of our funding arrangements, this work remains unpublished. Show less

    • Australia
    • Higher Education
    • 700 & Above Employee
    • Doctoral Student
      • 2000 - 2006

      Title: Cyclic Peptide Mimetics of Brain-Derived Neurotrophic Factor Supervisor: A/Prof Richard. A. Hughes Examiners: Prof I.A. Smith (Then President Australian Peptide Society) Prof J. Martinez (Then President European Peptide Society) My PhD studies saw me designing small peptide mimetics of the neurotrophic protein BDNF with the hope of generating compounds to treat Parkinson’s disease. Working in a small lab at the time, I was responsible for all aspects of the project, starting from the design of cyclic peptides and their synthesis, purification and characterisation. Next, I examined their activity in primary cultures of embryonic chick sensory neurons, and plasma stability assays. Finally, I took our most promising lead molecule and prepared a series of lipidated analogues which I examined in the “Caco-2 model” of the intestinal barrier. Since my time in the lab the lead molecule I developed has shown promise in several in vivo models of multiple sclerosis. Show less

Education

  • University of Melbourne
    Doctor of Philosophy - PhD, Pharmacology
  • University of Melbourne
    Bachelor of Science (Hons.), Pharmacology

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