The structural basis of disease

2nd March 2015.
Annalisa Pastore, King's College, London.

The 2nd Carlo Moreschi lecture will be given on the 2nd of March 2015 by Annalisa Pastore. The poster of the lecture can be downloaded here.

The availability of the full human genome as well as of those of several other organisms has open tremendous possibilities which we need to exploit to increase our knowledge in biology, medicine and any other related field. However, even when protein sequence is known we may still be a long way away from understanding function. In this lecture, I will discuss an example in which “function-hunting” has allowed us to understand, over a period of almost twenty years, the cellular role of a protein and its involvement in disease. Using different in silico, in vitro and in vivo methodologies, we have been able to determine the localization, structure and network of interactions of frataxin, the protein responsible for Friedreich’s ataxia. I will also show how the same approach can be generalized and suggest therapeutic interventions for other diseases.

Carlo Moreschi was born in Cermenate (Como) in 1876 and studied Medicine at the University of Pavia (1894-1900) and Collegio Borromeo (1896-1900). He worked in C Golgi’s laboratory as an undergraduate and published studies on experimental typhoid fever as early as 1900. After graduation he joined the University Clinic and continued his research on infectious disease and immunological reactions under Luigi Devoto. In 1904 he moved to the Institute of Hygiene of the University of Königsberg to work with Robert Pfeiffer, who had isolated H influenzae in 1892.  He worked in Germany, except for brief periods of times in which he returned to Pavia, until 1909 spending the last two years in Paul Ehrlich laboratory in Frankfurt and contributing to studies on tumour growth. After returning to Pavia in 1909/10 he joined the University Clinic directed by Vittorio Ascoli and shifted his interests to leukaemias. He joined the Army during World War 1 as a medical officer. He obtained a fixed-term contract at the University of Sassari (Sardinia) in 1916 and a tenured position in Messina in 1920 where he set himself the ambitious task of building a new Clinic and research laboratories. In 1921, however, aged 45, he contracted smallpox and died in in Pavia assisted by his close friend Emilio Veratti whom he had known since the undergraduate years in C Golgi’s laboratory. Carlo Moreschi studied extensively key components of soluble immunity, such as complement, and a range of immunological phenomena - such as agglutination and complement fixation - and their application to the diagnosis of infectious diseases (serology).  Further, in a key paper that he published in 1908 he described the anti-globulin reaction (Neue Tatsachen über die Blutkörperchenagglutination in Zentralblatt Bakteriol 46:49-51 (1908).  He is the main pioneer of immunological research in Italy. He married Carlotta Mühsam in 1909 and had two children.

Annalisa Pastore, the second Carlo Moreschi lecturer, is full professor also at King’s College London. She has been a structural biologist for more than 25 years and has a long-standing expertise in protein structure characterization and determination. Having studied in Naples, she worked as a post-doc in the groups of the Nobel Laureate R. Ernst (ETH, Zurich) and of Prof. I. D. Campbell (University of Oxford). In 1988. she moved to the European Molecular Biology Laboratory in Heidelberg, Germany where she established the first NMR laboratory and was appointed as the second women group leader. In 1997-2013, she worked at the MRC National Institute of Medical Research. More recently she moved to King’s College London where she works at the Wohl Institute. Her group focuses on the structural/functional characterization of proteins involved in neurodegeneration with the goal of understanding the non-pathologic cellular role of the responsible proteins responsible and describing the mechanisms that lead to pathology. Her research involves a wide range of biochemical, biophysical and structural methods. In 2000 AP was elected EMBO member and in 2013 member of the Academia Europaea. She has been recipient of several prizes and other recognitions and author of more than 220 peer reviewed articles.


You are here: Home Articles Lectures The structural basis of disease