2018Health6
| Ref. 2018Health6 | On-line application form |
| Supervisor name and surname: Iñigo Lasa | Supervisor mail: |
Description of the research project: The indiscriminately use of antibiotics has led to the rapid emergence of multidrug resistant bacteria that are referred to as “superbugs” and that cause infections that are untreatable. Unless action is taken to halt this problem we are facing the prospect of returning to a preantibiotic era. The World Health Organization published in 2017 a list of antibiotic-resistant "priority pathogens"; that is a catalogue of twelve families of bacteria that pose the greatest threat to human health, including methicillin resistant Staphylococcus aureus (MRSA). MRSA is a leading cause of bacterial infections worldwide, ranging from minor skin and soft tissue infections to severe conditions such as bacteraemia and infective endocarditis. MRSA strains are resistant not only to methicillin but also to other commonly used antibiotics. As a consequence, people with MRSA are estimated to be 64% more likely to die than people with a non-resistant form of the infection. Thus, it is essential to identify new drug targets and develop novel therapies to ensure effective treatments for people infected with MRSA. In this project we propose to use the major S. aureus signalling network as a novel target for the development of new antibacterials. This network is based on systems referred to as “Two Component Systems” (TCS) and formed by two proteins, one sensing the environment and the other responding accordingly, by changing the expression of specific genes in the bacterium. It is known that pathogenic bacteria use TCSs as a main mechanism for survival and establishment within the host. Importantly, TCSs are not present in mammal cells and thus, they are attractive target candidates for the development of new antimicrobials since their use would not have side effects in human cells. S.aureus has sixteen TCSs that allow it to survive in multiple environmental conditions and infect the host. Therefore, TCSs blocking would cause a decrease in virulence and also an inhibitory effect in S. aureus growth. In our laboratory, we have deciphered the complete regulon of each TCS present in S. aureus, that is, we have unravelled all changes in gene expression caused by the activation of every TCS. With this information, in the present project, we will be able to engineer a collection of S. aureus cells that will act as biosensors of the activity of each TCS. These biosensors will be used to analyze libraries of thousands of natural and synthetic compounds for the discovery of new antimicrobials that might be used on their own or synergically with known antibiotics. This topic of research is very attractive for future collaborative research between academia and industry. Hence, we count on present collaborations with biotech companies, such as Recombina Biotech or Biomar Microbial Technologies, and highly recognized international research groups for external training and the success of this project. The research project is completely linked to the “INFECMOL” Action Plan of Campus Iberus, whose main objective is to identify new compounds with antimicrobial activity to combat infectious illnesses in a personalized manner. The successful candidate should have knowledge in bioinformatics and microbiology and should be eager to learn new methods. | |
PHD Programme: | |
Supervisor short biography: Professor of Microbiology of the Public University of Navarra (Pamplona, Spain). Director of Navarrabiomed Biomedical Research Center. Research ID: F-2947-2011; Scopus ID: 7003887382 Ph.D. Theses directed: 13 Scientific Publications (WOK, 6th August 2018): 101 Citations (Scopus, 6th August 2018): 5876 H-index (Scopus, 6th August 2018): 45 | |
Title of the research project: Novel therapies for the treatment of methicillin-resistant Staphylococcus aureus infections | |
Gross annual salary: 22.000-26.000 € | |
Working hours: | Dedication: |