Università degli Studi di Milano
Dottorato di Ricerca in Medicina Molecolare e Traslazionale
29 Settembre 2015
Aula Magna, settore didattico,
Palazzo LITA, via F.lli Cervi 93, 20090
Segrate
Dalle 10.45 alle 12 :Nanotechnology and
proteomics: better diagnostics and better
therapeutics in the era of personalized medicine
Relatrice : Dr.sa Alessandra Luchinia
a
Center for Applied Proteomics and Molecular Medicine - George Mason University
a seguire discussione
Dalle 12.15 alle 13.00: Nanoparticle enhanced
urinary antigen test for the detection of Lyme
Borreliosis
Relatore : Dr. Ruben Magni
a
a,b
Center for Applied Proteomics and Molecular Medicine - George Mason
University, bMMT PhD Student Università di Milan
a seguire discussione
Studenti, dottorandi e colleghi sono invitati a partecipare numerosi
Organizzazione a cura di Cristina Battaglia
La partecipazione è aperta e gratuita.
Per informazioni : [email protected]
Palazzo LITA, Via F.lli Cervi, 93 – 20090 Segrate, Italy
Tel +39 02 503 40421; e-mail :[email protected]
Università degli Studi di Milano
Dottorato di Ricerca in Medicina Molecolare e Traslazionale
Nanotechnology and proteomics: better diagnostics and better
therapeutics in the era of personalized medicine
Alessandra Luchini
Abstract:
Many low abundance biomarkers for early detection of cancer and other diseases are invisible
to mass spectrometry because they exist in body fluids in very low concentrations, are masked by high
abundance proteins such as albumin and immunoglobulins, and are very labile. To overcome these
barriers, we created porous, buoyant, hydrogel nanoparticles containing novel high affinity (K D <10-13
M) chemical baits for protein and peptide harvesting, concentration, and preservation in body fluids.
Particles are mixed with body fluids and target analytes are captured with high affinity by baits
immobilized in the particles. The nanoparticles can achieve a 10,000 fold effective amplification of
the analyte concentration, enabling mass spectrometry (MS) discovery of candidate biomarkers that
were previously undetectable. This nanotechnology was applied to a unique collection of plasma
samples (case-control study nested in the Physician Health Study) in order to identify biomarkers that
predict the risk of Non-Small Cell Lung Cancer (NSCLC). The nanoparticles are currently used for
novel high sensitivity urinary antigen tests for tuberculosis, Chagas disease and Lyme disease.
We use the same high affinity, organic dyes as “molecular paints” for a new method to
identify “hot-spots” of protein-protein interaction that constitute important drug targets. Our chemistry
employs a new principle of solvent exclusion to functionally identify residues in hot-spot regions that
are most tightly associated. The surface of native preformed protein-protein complexes in solution is
rapidly coated by the paint chemistries that are administered in a pulse. Following processing for mass
spectrometry, only the solvent inaccessible residues of the preformed complex emerge from the tryptic
peptide sequence. We use this chemistry to sequence hot-spot domains between the three-way
interaction of IL1b ligand, its receptor IL1R1, and the accessory protein IL1RAcP and use this
information to create a novel hot-spot mimic peptides and monoclonal antibodies that block the
interaction, and suppress IL1b cell signaling.
Palazzo LITA, Via F.lli Cervi, 93 – 20090 Segrate, Italy
Tel +39 02 503 40421; e-mail :[email protected]