[SSS] Phage display technology: antibody production

Title: Phage display technology: antibody production

Speaker: Zélia Gouveia

From: Inflammation, IGC

Background:

Zélia Gouveia graduated from Biochemistry in Faculdade de Ciências da Universidade de Lisboa and joined the Inflammation Laboratory in 2010 where she is currently in the 4^th year of her PhD Thesis.

 Zélia Gouveia´s major interest is to understand the biological role of heme once release from hemoproteins, a common event in the pathogenesis of immune mediated inflammatory diseases. Heme, iron (Fe) protoporphyrin IX, functions as a prosthetic group in a range of hemoproteins essential to support life. The Fe contained within these prosthetic heme groups can catalyze the production of cytotoxic reactive oxygen species, through the Fenton chemistry. Presumably for this reason, heme must be sequestered within the heme pockets of hemoproteins, controlling its reactivity. However, under pathologic conditions associated with oxidative stress, some hemoproteins can release their prosthetic heme groups. While this heme is not necessarily damaging per se, it becomes cytotoxic in the presence of a range of inflammatory mediators. This can lead to tissue damage and, as such, exacerbate the pathologic outcome of several immune mediated inflammatory conditions. We have shown this to be the case in the context of severe forms of malaria, the disease caused by Plasmodium infection, as well as severe sepsis caused by polymicrobial infections.

The project developed by Zélia Gouveia aims at developing methodologies that allow discriminating and quantifying free heme, that is heme no longer bound to the heme pockest of hemoproteins, or methodologies that provides information on the molecular environment of heme after its release from hemoproteins. For that purpose, Zélia is using a phage library display technology to indentify single domain antibody fragments (sdAbs) targeting specifically “free heme”. She is currently exploring whether these sdAbs can be used to modulate the biologic effects of “free heme”, such as to prevent the pathogenesis of immune mediated inflammatory diseases. Furthermore, Zélia Gouveia aims at using these sdAbs in the diagnosis of life-threatening forms of severe sepsis and severe forms of malaria.