A novel antigen-specific platform for the treatment of organ-specific and systemic autoimmunity
- Postdoctoral Research Fellow
- Hours of work:
- 37.5 hours per week (excluding lunch hours)
- Annual leave:
- 24 days per annum plus statutory days
- C/ Villarroel 170, 08036 BARCELONA
- Accountable to:
- Drs. Pau Serra and Pere Santamaria
- Up to 3 years, by IDIBAPS
- 38.000 € plus housing facilities
RESEARCH LINE NO LONGER AVAILABLE
1. A postdoctoral position is available in the laboratory of Drs. P. Santamaria and P. Serra. The candidate will work with a team of scientists studying a new therapeutic approach in autoimmunity. The program is a continuation of work recently published in Immunity, 32:568-580, 2010, which has provided a nanovaccine-based approach for the treatment of type I diabetes.
Briefly, soluble peptides can induce peptide-specific T-cell tolerance, but cannot blunt poly-specific autoimmune responses, suggesting that therapeutic success might require deletion of multiple antigenic specificities at once. Because peptides are more tolerogenic when bound to MHC molecules on costimulation-impaired antigen-presenting cells than in solution, we envisioned that simultaneous delivery of several different type 1 diabetes (T1D)-relevant peptide–MHC (pMHC) complexes by nanoparticles (NPs) would enable the type of combinatorial autoantigen therapy needed to blunt T1D. We found that mono-specific pMHC-NP therapy was able to both blunt T1D progression in pre-diabetic NOD mice, and restore normoglycemia in diabetic animals. Most surprisingly, we found that pMHC-NP therapy functions by expanding, in an epitope-specific manner, autoantigen-experienced autoreactive CD8+ cells that suppress the recruitment of other autoantigenic specificities. Notably, we have shown that this therapeutic avenue exploits a new paradigm in the progression of chronic autoimmune responses that enables the rational design of disease-specific 'nanovaccines' capable of blunting autoimmunity without impairing systemic immunity, a long sought-after goal in the therapy of these disorders.
Our overall objective is to demonstrate that pMHC-coated NPs represent a realistic approach to expand autoregulatory T-cell memory in vivo in a disease- and organ-specific manner, as a essential step towards the translation of this therapeutic avenue for the treatment of several other autoimmune disorders.
2. The project is likely to involve some or all of the following techniques:
- General experimental techniques with mice
- Mouse transgenesis
- Confocal Microscopy
- Flow cytometry
- Common cellular and molecular biology techniques
The candidate primary focus will be in the formulation and testing of an experimental nanovaccine for Systemic Lupus Erythematosus in animal models of this disease.
Duties and Responsabilities
- To contribute to the design and planning of experiments in relation to this project
- To develop a thorough understanding of the research field and be involved in the intellectual decision making process required for successful completion of the project
- To set up and run experiments in consultation with the Principal Investigator
- To record, analyse and write up the results of experiments and ensure that laboratory notebooks are kept fully up to date as a formal record of the research
- To prepare and present findings of research to the Principal Investigator and other members of the centre
- To prepare progress reports on research
- The post holder may be required to perform some limited teaching and/or supervision of other members of staff and/or students, under the guidance of the Principal Investigator
- Responsible for ensuring that designated equipment is safe and maintained in good working order
- As duties and responsibilities change, the job description will be reviewed and amended in consultation with the post holder
- The post holder will carry out any other duties that are within the scope, spirit and purpose of the job, as requested by the Principal Investigator
Knowledge and Qualifications
- Undergraduate degree in a life science discipline.
- PhD in an appropriate life science discipline
- Accredited knowledge and skills in Immunology.
- Proficiency in English language.
- Research stay outside the country of residence.
- Publications in high impact factor peer reviewed journals.
- It is expected a thorough background on cellular and molecular biology, and experience working with animal models (rodents), chemistry, particularly nanoparticle chemistry, and a clear interest in immunology. In addition, it will be important to show ability to develop ideas logically and design experiments to test hypotheses, ability to modify and apply new methods to advance a project, and to analyse and write up data for presentations and publications.
- The post-doc should have a personal resume showing ability to present complex information effectively to a range of audiences and to write effective written and verbal communication skills.
- Ability to direct junior members of the laboratory in simple laboratory procedures
Experience and Personal Qualities
- Experience of working in a research environment and commitment to high quality research
- Experience in multi-disciplinary working and clear interest in working as part of the team. All the members of the team will collaborate in this research project.
- Ability to work independently and to use own initiative when required.