Background: Bioconjugation means the covalent derivatization of a biologically active (macro)molecule with a synthetic structure, which aims to improve its pharmacokinetics, and often is used to confer additional biological recognition (=targeting) and/or to liberate the active under precise environmental conditions. The most common example of bioconjugation is the PEGylation of proteins/peptides.
Description: This project aims to increase stability and to provide precise (cellular and sub-cellular) targeting capacity to actives such as RNA aptamers. This will be obtained by the means of the conjugation to artificial structures (e.g. soluble polymers [1], nanoparticles [2,3]), which will target the actives to the appropriate cellular environment, delivering them in response to a combination of signals [1,4]. The PhD candidate will develop skills in advanced synthesis and nanocharacterization, and in vitro and in vivo evaluation, interacting with groups in the areas of RNA biology and modelling, and in vivo pharmacology.
References: [1] V. Quagliariello, . N. Tirelli*, “Double-responsive hyaluronic acid-based prodrugs for efficient tumour targeting” Materials Science & Engineering C, 130 (2021) 112475 DOI:10.1016/j.msec.2021.112475. [2] A. Pisani, … N. Tirelli*, G. Bardi*, “CXCL12-PLGA/Pluronic nanoparticle internalization abrogates CXCR4-mediated cell migration” Nanomaterials, 10(11) (2020) 2304, DOI: 10.3390/nano10112304. [3] M. Geven, … N. Tirelli*, “Disulfide-mediated bioconjugation. How to control their formation and re-structuring on nanoparticle surfaces”, ACS Applied Materials and Interfaces, 11 (2019) 26607-26618. DOI: 10.1021/acsami.9b07972. [4] A. Gennari, … N. Tirelli* “Revisiting boronate/diol complexation as a double stimulus-responsive bioconjugation”, Bioconjugate Chemistry, 28 (2017), 1391-1402 DOI: 10.1021/acs.bioconjchem.7b00080
Main supervisor: Nicola Tirelli (Polymers and Biomaterials).
Essential expertise:
i. Undergraduate degree in pharmaceutical chemistry, or chemistry or biomedical engineering;
ii. General experience in organic synthesis (beyond bioconjugation);
iii. Experience in the use of chromatographic techniques;
iv. Specific experience in bioconjugation reactions.
Desirable expertise:
i. Experience in polymer synthesis and/or characterization
ii. Experience in cell culture
iii. Experience in flow (e.g. microfluidic) and/or solid phase synthesis
iv. Experience in nanomaterial characterization
How to apply. Prospective students must submit using the online form the following documents
1) 2-page CV, which includes studies, expertise and achievements.
2) 1-page research statement, which includes the choice of a project from the list above and a justification of the choice. Only if robustly justified, the student may signal their interest also for a second project, but there is no guarantee that this will be taken into account by the selection panel.
3) A transcript of undergraduate and postgraduate studies.
4) A valid IELTS certificate, obtained no more than two years before the proposed registration date.
5) Contact details of two referees.
Deadline for application: 14th of February 2022.