One Early Stage Researcher (PhD students) position at the University of Padova within the framework...

Updated: about 1 month ago
Job Type: FullTime
Deadline: 15 Nov 2021

One ESR position (PhD) is now available at the University of Padova (Italy), within theframework of the Maria Skłodowska-Curie Innovative Training Network (MSCA-ITN) project “Directing the immune response through designed nanomaterials"- DIRNANO.

Hosting department: 

ESR position (code ESR02):Department of Biomedical Sciences.

WARNING: if you wish to apply, please remember to upload the file named "Application form" (available here: ALBO DIPARTIMENTO DI SCIENZE BIOMEDICHE ) duly signed and dated. The application form should be uploaded in the section "Other Attachments" of the online procedure that starts in this job vacancy at the section "where to apply".

ESR02- Overview of the hosting Department and Individual research project.

The scientific activities of the Department of Biomedical Sciences (DBS) of the University of Padova (Italy) (http://www.biomed.unipd.it/ ), launched on March 1, 1992, focus on those major different and complementary aspects of cellular and molecular biology, cell physiology, molecular pathology and experimental pharmacology having implications for genetics diseases and degenerative, inflammatory processes, malignancies and their diagnosis/cure perspectives on a molecular-based ground. The research on the many physio-pathological multifaceted effects, implications and mechanisms of the newly emerged integrated discipline of NANO(BIO)MEDICINE gained its place within the general investigation milieu of the Department in the past decades, and is steadily progressing in the departmental scientific area dedicated to Medical Biotechnology.

One ESR position (ESR02) is now available at the Department of Biomedical Sciences.

The ESR2 of NANO-BIOTECHNOLOGY AND NANO-BIOMEDICINE of the DBS, led by Prof. Emanuele Papini, and the Marie Skłodowska - Curie Innovative Training Network (MSCA-ITN) project “DIRNANO - Directing the immune response through designed nanomaterials” OFFERS an Early Stage Researcher (PhD Student) position:

ESR02 - "Protein composition and functional effects of the species-specific biomolecular corona formation on NPs”.

-This PhD project will focus on the full characterization of the interaction between host macromolecules and consortium-generated NPs in host fluids to understand their influence on NP bioactivity and efficacy.

-This will be done in closely related mammalian species used as preclinical models (e.g. mouse and pigs), which evolved differentiated reactivity and organization of Complement and other innate mechanisms, which could negatively impact extrapolations to the human being.

-The goal of this ESR is extensively mapping the corona composition formed in human and animals’ sera, according to the coat type and evaluating Ca /Mg dependence to monitor complement activation and abundance. We will probe the effect of putative pro-opsonic agonists (e.g. collectins) with antagonists (e.g. N-acetyl-glucosamine or mannose) or compound mimicking monomers of the NP-covering polymers (e.g. N,N-dimethyl acetyl-amide in case of PMOXA coats) on NP proteome and phagocytes capture.

-The effect of anti-corona protein mab (native or engineered) or recombinant engineered coat-binding innate proteins (e.g. Ficolins, C1q) will be assayed to increase the number of conditions studied and the robustness of quantification and to considerably reduce times. After initial protein abundance screening by label-free parameters, major and functionally relevant components will be assessed by quantitative proteomics approaches or WB.

-In case of commercial antibodies lack, polyclonal/monoclonal ab will be generated by another participant to the project, the company STABVIDA.

-Recombinant antibodies-based assays will be also applied for validation, to immune -deplete sera and to test biochemical and functional effects. Modulation of the binding of specific components to a coat will be also obtained via use of known innate-recognized sugars or by using single molecules resembling the NP polymer coats unit (for example dimethyl amide for PMOXA). Phagocytosis will be quantified by FACS and confocal analysis.

Expected results of ESR02 activity:

Providing information on the major functional pro-opsonic and pro-inflammatory innate component affinity to coats type and suggesting feed-back modification of their formulation to test the possibility of its abolition (stealth) or improvement (nanovaccine). Reveal major species-specific molecular differences and point to NP characteristics showing interspecific similarity, for safer preclinical predictive power.

ESR02 International collaborations and secondments are foreseen in:

  • The Department of Tumor Biology and the Department of Molecular Cell Biology of the Oslo University, Oslo, Norway (OUS, under the supervision of prof. G.M. Malandsom), to learn TAM targeting in murine models to allow training in methodologies used to assess in vivo distribution of NPs and on the evaluation of selective capture to defined TAM phenotype, month 12, 3 months.
  • The Department of Biosciences of Paris Londron University, Salzburg, Austria (PLUS, under the supervision of prof. J. Horeis-Hoeck) to be trained on the capture analysis of macrophage related but functionally different antigen presenting cells, like DCs, month 24, 3 months.
  • The ESR02 will be employed and enrolled in the doctoral programme of Biomedical Science (PhD Biomedical Sciences) of the University of Padova.

    For further information about the scientific content please contact the principal supervisor: Prof. Emanuele Papini (emanuele.papini@unipd.it and in CC dirnano.euproject@bio.unipd.it )

    PROJECT AND CONSORTIUM DESCRIPTION

    DIRNANO is a European Training Network funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curiegrant agreement No. 956544.

    The consortium comprises universities, research institutions, enterprises and partner organisations in 9 European countries (Norway, the UK, the Netherland, Spain, Portugal, Italy, the Helvetic Confederation, Austria and Hungary). This creates a novel platform for training a network of 15 Early Stage Researchers (ESRs) in the fields of nanomedicine, nanopharmacology, nanobiotechnology and nanomaterials for medical applications.

    DIRNANO Scientific target: It is known that the full therapeutic potential of nanomedicines is unfulfilled due to opposing interactions with body’s defenses and adverse immune reactions. DIRNANO aims at overcoming these limitations through the comprehensive understanding of nanomaterials-host interplay and an extensive animal model testing.

    We will develop strategies to map, study, modulate and exploit nanoparticle (NP)-immune interactions through core state-of-the-art approaches.

    These include:

  • inception of novel, but simple, coating engineering based on new organic polymers and conjugation chemistry, rational polymer pairing and zwitterionic lipids.
  • engineering (with a green-chemistry approach) of libraries of host or microbial derived modulators of the innate immunity (particularly of the complement system)
  • designing and pre-clinical testing of next generation therapeutic nanovaccines (i.e. NPs with optimized multivalent neo-antigen presentation and immunostimulatory cues) and immune- modulating NPs directly targeting tumor cells or immune suppressive cells.
  • The DIRNANO’s core-scientific training is focused on gross structure- activity profiling, integrating interfacial and chemical sciences with systems immunology for mapping of dynamic host and interfacial factors that regulate NP performance This approach will lead to rational engineering of libraries of on-demand NPs with tunable immune modulating functions Moreover, the combinatorial analysis of NP core-coat scaffold will improve our temporal and spatial understanding of biomaterial-innate immune interactions at a deeper molecular level, and potentially fill the void in overcoming adverse injection reactions to nanopharmaceuticals in sensitive individuals.

    The participating teams comprise internationally renowned scientists and industrialists at the forefront of nanomedicine, immune safety, pharmaceutical sciences, green chemistry, commerce and business, where many of the participants have a proven record of accomplishment and working with each other.

    ESR training and final achieved competences. The ESR will be engaged in an integrated and highly interdisciplinary approach for academic and regulatory/business training having a broader cutting-edge knowledge in translational nanomedicine bioengineering.ESRs will master immune safe-by-design and pharmaceutically viable smart-by-design approaches to lead the development of the future nanopharmaceuticals through a low-risk-high gain perspective.

    ESR future mission. DIRNANO ESRs will be part of a unique pan-European macro-environment for integrated, advanced and accelerated training and circulation through open innovation and outreach activities at the highest international level, thereby contributing to the European socioeconomics and education values, skill retention and brain-gain.


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