Investigating Staphylococcus aureus - macrophage interactions during infection
Lead Research Organisation:
University of Warwick
Department Name: Warwick Medical School
Abstract
DTP 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 overview:
Staphylococcus aureus, a bacterium often found on our skin and nares, is one of the major causes for life threatening infections such as pneumonia and endocarditis and are frequently associated with healthcare systems. Hospital-associated S. aureus infections have been responsible for increasing healthcare costs globally. The rise of new antibiotic resistant strains has been a major hurdle in effective treatment of S. aureus infections with the available drug therapies, and we do not currently have a vaccine against staphylococcal infections.
S. aureus is known to closely interact with our cells during infection. In addition to acting from outside cells, S. aureus can enter inside our cells using it as a niche to multiply. Immune cells called macrophages, which form the first line of defence, are important in pathogen clearance. However, studies have indicated that these cells are not always effective in killing S. aureus. S. aureus is able to survive and multiply within macrophages, which then inadvertently aid in transporting bacteria to other body sites. We do not currently have a good understanding of the bacterial proteins and pathways that this pathogen uses to manipulate our immune cells.
S. aureus exports several factors to the external environment during infection. It contains a specialized protein export system called the type VII secretion system (T7SS), which secretes proteins that are important for virulence of the bacterium, and good vaccine candidates. The precise biological functions of these proteins during infection are not known. Our recent research demonstrated that the T7SS proteins can control macrophage death. However, we do not understand how these proteins interfere with pathways inside cells or with our immune responses to this pathogen.
The main goals of this project are to understand how S. aureus manipulates macrophage killing and how this impacts staphylococcal infection outcomes. We will examine how the T7SS proteins interfere in host signalling pathways using a combination of high-resolution imaging, cellular and immunological assays to identify pathways that interact with the T7SS. High throughput sequencing approaches applied to in vitro infection models along with in vivo infection models will help identify specific immune mechanisms involved in S. aureus infection.
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 overview:
Staphylococcus aureus, a bacterium often found on our skin and nares, is one of the major causes for life threatening infections such as pneumonia and endocarditis and are frequently associated with healthcare systems. Hospital-associated S. aureus infections have been responsible for increasing healthcare costs globally. The rise of new antibiotic resistant strains has been a major hurdle in effective treatment of S. aureus infections with the available drug therapies, and we do not currently have a vaccine against staphylococcal infections.
S. aureus is known to closely interact with our cells during infection. In addition to acting from outside cells, S. aureus can enter inside our cells using it as a niche to multiply. Immune cells called macrophages, which form the first line of defence, are important in pathogen clearance. However, studies have indicated that these cells are not always effective in killing S. aureus. S. aureus is able to survive and multiply within macrophages, which then inadvertently aid in transporting bacteria to other body sites. We do not currently have a good understanding of the bacterial proteins and pathways that this pathogen uses to manipulate our immune cells.
S. aureus exports several factors to the external environment during infection. It contains a specialized protein export system called the type VII secretion system (T7SS), which secretes proteins that are important for virulence of the bacterium, and good vaccine candidates. The precise biological functions of these proteins during infection are not known. Our recent research demonstrated that the T7SS proteins can control macrophage death. However, we do not understand how these proteins interfere with pathways inside cells or with our immune responses to this pathogen.
The main goals of this project are to understand how S. aureus manipulates macrophage killing and how this impacts staphylococcal infection outcomes. We will examine how the T7SS proteins interfere in host signalling pathways using a combination of high-resolution imaging, cellular and immunological assays to identify pathways that interact with the T7SS. High throughput sequencing approaches applied to in vitro infection models along with in vivo infection models will help identify specific immune mechanisms involved in S. aureus infection.
Organisations
People |
ORCID iD |
| Meera Unnikrishnan (Primary Supervisor) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N014294/1 | 01/10/2016 | 30/09/2025 | |||
| 2430038 | Studentship | MR/N014294/1 | 05/10/2020 | 30/09/2024 |