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Molecular mechanisms underlying endothelial dysfunction in neonatal sepsis

Coordinator Drª Prescilla Emy Nagao

 

Sepsis is responsible for 2.9 milions of deaths/year, reaching 50% of mortality in Brazil. Streptococcus agalactiae is the major cause of neonatal sepsis, which often leads to death or long term complications. A major limitation in our current understanding of how bacteria interact with endothelial cells from the fact that previous studies have been carried out under static conditions.

 

The 3D model criated by Dr. Kerrigan (Royal College of Surgeons in Ireland) is unique and capable to create the vascular biochemical enviroment, containing the endothelium layers, smooth muscle, collagen and elastine. The proposal is that we improve the basic understanding of the host response to S. agalactiae infection in order to develop a therapy that could surpass current interventions in the clinic for the treatment of neonatal sepsis.

 

The project proposed has innovation in the area of studies on pathogen-host interactions, since the current knowledge was mostly achieved through in vitro cell culture techniques in a static 2D model. Dr Kerrigan has developed a dynamic 3D cell model capable of mimetizing the blood vessel in vivo.

 

Both supervisors (Dr Kerrigan and Dr Nagao) have expertise in the area and also a good collaborative relationship, which makes it more advantageous for the development of this Project. The Royal College of Surgeons in Ireland (RCSI) has an international reputation for making significant advances in several investigative areas including host infection and bioengineering. Dr Kerrigan is a principal investigator in both the Host infection Group and the Bioengineering Group in RCSI and has led the way for bringing together a multidisciplinary group of researchers to further advance our knowledge in the area of vascular infection.

 

RCSI has many national and international links and its involvement in molecular medicine puts the RCSI at the forefront of biomedical research. RCSI is well funded, with state-of-the-art laboratories making it very well equipped to carry out the proposed project. It has a strong research team, with diverse expertise, fostering a multidisciplinary research environment.

 

RCSI is committed to translational research. In order to ensure success in translation all projects have strong links with world class clinicians who act as advisors in research projects. The project proposed here will focus on a unique method for developing a clinically relevant model of infection of the bloodstream which we strongly believe will lead to an improved therapeutic modality for the treatment of sepsis.