Isolation and characterization of novel microbial natural products that activate autophagy
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 hypothesis-led biomedical research questions. 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:
Autophagy, which literally means 'self-eating', is an essential process that involves the degradation of cytoplasmic material. This homeostatic process enables cells to reutilise materials and produce energy when conditions become unfavourable or to clear damaged cellular components or remove specific proteins if they are over-produced. Dysfunction in autophagy has been implicated in many diseases such as cancer and bacterial and viral infections. Autophagic activity declines with age and so has been associated with the development of age-related diseases, such as neurodegeneration. It is thus important to develop interventions that maintain autophagic activity through the life course. Natural products from Streptomyces bacteria produce many metabolites of therapeutic interest. For example, Rapamycin is a natural product from Streptomyces that induces autophagy. However, Rapamycin also has unwanted side effects such as immunosuppression. Thus, there is a need to identify additional natural compounds that can be produced in large quantities but without lack such side effects. The aim of this project is to isolate and characterize additional novel natural compounds that can activate autophagy. Specifically, the student will Isolate novel natural compounds from diverse culture extracts prepared using Streptomyces species using a range of analytical chemistry techniques including LC-MS, HPLC and NMR spectroscopy for structural elucidation, combined with bioinformatics to predict the nature of the compounds of interest. The student will then test if these compounds activate autophagy in larva and adult flies of Drosophila models of human neurodegenerative disease. The molecular and cellular pathways stimulated by pro-autophagic compounds will be characterized further in mammalian tissue culture cells.
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 hypothesis-led biomedical research questions. 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:
Autophagy, which literally means 'self-eating', is an essential process that involves the degradation of cytoplasmic material. This homeostatic process enables cells to reutilise materials and produce energy when conditions become unfavourable or to clear damaged cellular components or remove specific proteins if they are over-produced. Dysfunction in autophagy has been implicated in many diseases such as cancer and bacterial and viral infections. Autophagic activity declines with age and so has been associated with the development of age-related diseases, such as neurodegeneration. It is thus important to develop interventions that maintain autophagic activity through the life course. Natural products from Streptomyces bacteria produce many metabolites of therapeutic interest. For example, Rapamycin is a natural product from Streptomyces that induces autophagy. However, Rapamycin also has unwanted side effects such as immunosuppression. Thus, there is a need to identify additional natural compounds that can be produced in large quantities but without lack such side effects. The aim of this project is to isolate and characterize additional novel natural compounds that can activate autophagy. Specifically, the student will Isolate novel natural compounds from diverse culture extracts prepared using Streptomyces species using a range of analytical chemistry techniques including LC-MS, HPLC and NMR spectroscopy for structural elucidation, combined with bioinformatics to predict the nature of the compounds of interest. The student will then test if these compounds activate autophagy in larva and adult flies of Drosophila models of human neurodegenerative disease. The molecular and cellular pathways stimulated by pro-autophagic compounds will be characterized further in mammalian tissue culture cells.
Organisations
People |
ORCID iD |
| Ioannis Nezis (Primary Supervisor) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N014294/1 | 01/10/2016 | 30/09/2025 | |||
| 1935848 | Studentship | MR/N014294/1 | 02/10/2017 | 20/03/2021 |