Development of Purine-based novel analgesics
Lead Research Organisation:
University of Warwick
Department Name: Warwick Medical School
Abstract
Programme overview:
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address important applied biomedical research questions in priority areas aligned with industry. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.
Project overview:
Chronic pain is a debilitating condition that has severe implications for the sufferer, their families and society in general in terms of health care costs and days and productivity lost to ill-health.
Whilst there are numerous pain medications available, some pain sufferers do not benefit from pain relief and/or suffer unacceptable adverse effects. This is particularly the case for opioid-based painkillers where the risk of dependence, addiction, abuse and death has contributed to what has been termed "the opioid crisis", and which has led to the deaths of tens of thousands of people in the USA and elsewhere. Novel treatments for the safe and effective management of pain are thus required for sufferers of these life-limiting conditions.
In this project, in collaboration with NeuroSolutions, a contract research organisation expert in pain and analgesia, we will investigate novel compounds, centred around molecules known as purines, that interfere with pain pathways to explore their cellular actions and therapeutic potential in an range of clinically-relevant models of pain. Importantly, these compounds, based upon a molecule whose highly unusual properties we discovered, have the potential to provide strong pain-killing, but without the cardiovascular and respiratory side effects previously observed with molecules targeting this particular biological process.
The project will involve novel organic synthetic chemistry through our collaborator in Switzerland; sophisticated molecular simulations of drug behaviour with a team at Coventry & Essex universities; detailed cellular characterisation of the actions of these drugs in simplified cellular systems with colleagues at Cambridge University, and in-depth examination of these molecules in both test-tube and whole animal assays of neuronal communication, cardiovascular and respiratory physiology, pain pathways, locomotion, addiction potential and sedation. All of these studies will be underpinned by rigorous quantitative assessment of the effects of these compounds in biological systems.
By the conclusion of this study we expect to have identified compounds with the potential for clinical trials in man.
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address important applied biomedical research questions in priority areas aligned with industry. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.
Project overview:
Chronic pain is a debilitating condition that has severe implications for the sufferer, their families and society in general in terms of health care costs and days and productivity lost to ill-health.
Whilst there are numerous pain medications available, some pain sufferers do not benefit from pain relief and/or suffer unacceptable adverse effects. This is particularly the case for opioid-based painkillers where the risk of dependence, addiction, abuse and death has contributed to what has been termed "the opioid crisis", and which has led to the deaths of tens of thousands of people in the USA and elsewhere. Novel treatments for the safe and effective management of pain are thus required for sufferers of these life-limiting conditions.
In this project, in collaboration with NeuroSolutions, a contract research organisation expert in pain and analgesia, we will investigate novel compounds, centred around molecules known as purines, that interfere with pain pathways to explore their cellular actions and therapeutic potential in an range of clinically-relevant models of pain. Importantly, these compounds, based upon a molecule whose highly unusual properties we discovered, have the potential to provide strong pain-killing, but without the cardiovascular and respiratory side effects previously observed with molecules targeting this particular biological process.
The project will involve novel organic synthetic chemistry through our collaborator in Switzerland; sophisticated molecular simulations of drug behaviour with a team at Coventry & Essex universities; detailed cellular characterisation of the actions of these drugs in simplified cellular systems with colleagues at Cambridge University, and in-depth examination of these molecules in both test-tube and whole animal assays of neuronal communication, cardiovascular and respiratory physiology, pain pathways, locomotion, addiction potential and sedation. All of these studies will be underpinned by rigorous quantitative assessment of the effects of these compounds in biological systems.
By the conclusion of this study we expect to have identified compounds with the potential for clinical trials in man.
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/R015910/1 | 01/10/2018 | 30/09/2026 | |||
| 2270402 | Studentship | MR/R015910/1 | 01/10/2019 | 11/06/2024 | Circé La Mache |