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Margaret’s story

Margaret’s story. Margaret was a chemistry MChem undergraduate student at the University of Leeds. She was particularly interested in organic synthesis and developing her understanding of how small molecules can modulate biological systems.

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Margaret’s story

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  1. Margaret’s story

  2. Margaret was a chemistry MChem undergraduate student at the University of Leeds. She was particularly interested in organic synthesis and developing her understanding of how small molecules can modulate biological systems. As a result, her choices of optional modules tended to be weighted towards medicinal- and biochemical topics.

  3. Whilst in her second year, Margaret spent two weeks carrying-out a practical project under the supervision of Peter, an academic staff member who was working on a collaborative project with GSKon new templates for interrupting protein-protein interactions. During this time, she happened to meet Bill from GSK who had had come-up to Leeds for a project meeting.

  4. During Margaret’s third year, she successfully secured an industrial placement position at Novartis. Although organic synthesis had been her main interest, her industrial placement was within the structural biology group where, supervised by Gill, she developed new skills in the area of protein purification and biophysical analysis.

  5. During one group meeting, where a new biophysical technique being pioneered by the group was discussed, Margaret remembered that some of the synthetic work within Peter’s group might be relevant. She put Gill and Peter in touch with one another and as a result, they put together a proposal for a BBSRC Industrial CASE award which has since been funded.

  6. Whilst the industrial placement at Novartis provided a superb environment for Margaret to learn a new area of science and also to develop a range of transferable research skills, it also helped to reinforce her conviction that organic synthesis was her main interest and she became even more determined to undertake postgraduate research in this area. After having achieved a first class degree, Margaret joined a synthesis team at Imperial College, London where she completed a PhD as part of an EPSRC-funded CASE award with AstraZeneca.

  7. During her 3 month industrial placement, she worked in the lab of her industrial supervisor Annette whose group were looking into new treatments for inflammation. While working there, Margaret spent some time with the Structural Biology group and was interested to learn from one of their team leaders, Steve, that they were developing similar biophysical methods to those she had been involved in during her undergraduate placement at Novartis. She suggested that Steve get in touch with Gill to see if there was any opportunity to share knowledge in this area. As a result of this contact, Steve and Gill now lead a precompetitive consortium developing new platforms for biophysical screening, funded by Innovative Medicines Initiative (IMI) and involving a wide range of partners from Pharma, CROs and academia.

  8. Margaret has also been involved in this consortium, providing synthetic expertise. During one consortium meeting, a fellow consortium member Jane from Edinburgh offered Margaret a post-doctoral position in her structural biology group which Margaret accepted.

  9. One year into her research in Jane’s group, Margaret gave a talk at Argenta where she presented on some of her most recent results. Julie at Argenta was particularly interested in one of the techniques Jane had developed and set-up a 1-year Knowledge Transfer Partnership project to establish whether the technique could be adapted to meet a specific programme they were running. Margaret was selected as the Associate for this programme, given her detailed knowledge of the technology but also because in interview, she came across as someone who understood the needs of industry and what would be required of her in terms of knowledge, skills and behaviours

  10. RSC-hosted workshop on permeability Three months into her KTP, Margaret became aware of a workshop that was being run by the Royal Society of Chemistry (and supported by a number of other professional bodies) that was looking to bring together people exchange fellows from a range of disciplines associated with medicines research. Although a little hesitant at first she was encouraged by Julie and also recalled the value network-building had brought to her academic career to date. The offer of a £3000 prize and grants for attendees to support further network-building and access to industry-based training convinced her even more that the event would be valuable and in the end, she decided to attend.

  11. The event opened Margaret’s eyes to the number of people exchange programmes available and she learned from a number of highly successful senior researchers from academia, industry and the NHS how ‘mobility’ had been such an important success factor in their careers. Having never before spent time with clinical researchers, she was especially excited by the conversation she had with Barbara, a clinical researcher from Nottingham who specialised in anti-inflammatory research and the two of them immediately struck-up a rapport. Barbara was particularly surprised to come across a chemist who had such a good understanding of the challenges and opportunities in inflammation, something she had learned during her CASE placement at AstraZeneca.

  12. When the time came during the workshop to form cross-disciplinary teams to tackle a drug discovery problem, Margaret and Barbara joined forces along with James. James was a pharmacology expert with over 10 years of industrial experience and who was engaged in a Royal Society Exchange Fellowship with Nottingham University. Barbara and James knew each other by sight but this workshop was the first time they had chatted to one another. The three of them formed a team, mentored by Adam, a clinical project manager from Pfizer. They spent the next morning sharing their knowledge and experience, eventually coming-up with a proposed solution that won them second prize of £1000

  13. Later that afternoon, Adam gave a presentation on the training that Pfizer could offer the workshop participants in the area of medicines regulation and safety evaluation. This was an area Margaret knew relatively little about and 3 months after the workshop, she submitted an application for a £250 mobility grant to attend the training. Her bid was successful and she attended the training, along with 2 other workshop attendees.

  14. The training was extremely valuable and made Margaret think about how her own research could help support clinical development programmes, in particular in the area of safety biomarkers. She shared her thoughts with Mike from Imperial College who worked in the Chemical Biology Group. He was pulling together a proposal for a new approach to biomarkers, particularly for pathways involving Protein-Protein interactions. This was in response to a call that had been established by Wellcome Trust and MRC to address an important, emerging area of medicines research. Mike was delighted to welcome Margaret to the team, with her wealth of experience in the area and Margaret also invited Bill to join. Bill had left GSK two years previously and had started-up his own spin-out company specialising in the design and synthesis of probes to investigate protein-protein interactions.

  15. The proposal was successful in securing funding – both Wellcometrust and MRC highlighted the exceptional quality of the proposal, the credibility and expertise of the individual scientists and the extensive network that they would bring to bear on such a challenging, multi-disciplinary project. Margaret has been working on this project for 3 years in a post that is co-funded by her host university (Bristol) and industry (GSK).

  16. Margaret’s network

  17. Multiple networks through people exchange programmes

  18. Expanding knowledge Developing skills Building networks Supporting career progression Building a highly networked medicines research community

  19. Summary of participants for Exchange Fellowship Workshop in Drug Discovery Medicinal chemistry (13) Biology (13) Clinical (13) Formulation/delivery (1)

  20. Summary of participants for Exchange Fellowship Workshop in Drug Discovery

  21. New Business Models • Industry-academia collaborations leading to longer term, sustainable partnerships

  22. Drug Discovery Pathways Group Partnership between RSC, SB, AMS, BPS, BiochemSoc (plus >15 additional learned societies/professional bodies) Organisational models Knowledge Skills

  23. Medicines Research Target Validation Target Validation Candidate nomination Clinical proof-of-concept Disease Specialists Chemists, Pharmacologists, Biochemists and Drug Metabolists Toxicologists, Formulation Scientists, Clinicians Right target Right compound Right study

  24. Medicines Research

  25. Attrition: Major cause of attrition is attributed to Phase 2 efficacy failure • Improve target/patient selection Duplication and redundancy: Small molecule research dependent on chemical tools • Precompetitive collaboration in target validation Fragmented model: Large Pharma dependent on in-licensing for around 50% of late stage portfolio • Professionalization of drug discovery in academia • Line-of-sight to patients Skills: Pharma downsizing results in lower training capacity • Window of opportunity to retain and develop world class talent Challenges and Opportunities

  26. Research benefit Permeability Career benefit

  27. Existing Schemes Partnership Award

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