During the first years of my training, I have worked in neurobiology, using my skills in fluorescence microscopy to dissect mechanisms underlying the biology or dysfunction of neurons.
I’ve soon realized that a scientist can get great satisfaction in basic research, yet focusing on questions that are relevant also to disease therefore increasing the probability that one’s findings may be impacting the lives of many.
In the aging society, indeed, research activities for the understanding of neurodegenerative diseases such as Parkinson’s (PD) and Alzeihmer’s disease (AD) are of fundamental importance. One of the major hallmarks of PD and AD is protein aggregation involving alpha-synuclein, A-beta peptide and the protein tau. During my PhD and some later work, I have studied of protein-protein interactions, aggregation and post-translational modifications of alpha-synuclein, a small protein linked to PD, but also of the protein Tau and the A-beta peptide involved in Alzheimer.
I was planning to resume work on alpha-synuclein, starting my own research project based on the hypothesis that alpha-synuclein is an adaptor protein that interacts with substrates to facilitate their interaction with membranes in a complementary manner to 14-3-3 proteins and their role within the cytoplasm. For this I needed to implement a technique that could visualize multiple homo- and hetero- interactions within the cell.
At the same time, a work published by Santos et al. in 2007 on MAPK network topology and cellular decision made be very interested to Network Biology where the techniques I was about to implement could have a very significant impact. Therefore, when offered to work on cancer biology with the techniques I had in mind to study molecular networks and how they encode for cellular decision, I accepted.
My passion for neurobiology is, however, not exhausted and I find two very important similarities between the neurosciences and network biology. First, of course, the brain is a network and encodes memories, functions and behaviour in this immense connectivity of individual cells. The brain of the cell is its own biochemical networks. Second, we know a lot about neurons and molecular mechanisms in neurobiology. We also know a lot about the behaviour of humans. However, we do not understand the link between these two worlds: molecular machineries and behaviour. Similarly, we know a lot about molecular mechanisms within the cell, cell signalling, metabolic networks and gene regulatory networks. We know a lot about cell function and their “behaviour” within the environment. However, we often do not understand how molecules encode for those behaviours, in particular during disease. Similar challenges in a way.
I joined the Univesity of Cambridge in 2008 to work on malaria research in the laboratories of Prof. Clemens Kaminski and Dr. Virgilio Lew. I thought to have a break from engineering technologies and biotechnologies to come back to more biophysical and biological work whilst reorganizing my thought to conceive what would be my future research programme. Despite this stint on malaria research was brief, it was succesful and permitted me to grow as a scientist.
Plasmodium falciparum (Pf) is the protozoan that causes the most fatal version of malaria, disease that affects a large part of the world population. Pf enters the blood stream of humans through the bite of the mosquito Anopheles and then penetrates into a red blood cell (RBC). Pf stays comparatively quiescently for about 20-25 hours before starting to pemeabilize the plasma membrane of the host and to digest haemoglobin at high rates. At about 45 hours post-invasion Pf initiates schizogony and generate 1-2 dozens daughter cells. This is the asexual cycle of Pf and it lasts 48 hours, during which the host cell undergoes significant alterations of its homeostasis.
In a series of papers, we have described how red blood cells chane volume, haemoglobin content and element concentrations during the life cycle of Pf, therefore permitting us to amend the existing numerical models for the homeostasis of infected RBCs.