Studying botulinum and tetanus neurotoxins in Italy

Alessandra Geffner-Smith '14

Alessandra Geffner-Smith ’14, Graduate Student

Major: Biochemistry

Graduate Program: Department of Biomedical Sciences, University of Padova;

During my undergraduate career at Mount Holyoke College, I was encouraged to be independent and to pursue my interests, leading me to the beginning of my present-day career in neurotoxin biomedical research. I began conducting research with botulinum neurotoxin my sophomore year, and have increased my passion for it ever since. During my college years, I presented posters of my research at international conferences where I met many leading scientists in the field including my now current P.I., Dr. Cesare Montecucco, head of the world’s foremost lab in clostridial toxin and neurodegenerative disease research at the University of Padova in Padova, Italy.

Following graduation with a biochemistry degree from Mount Holyoke, I immediately moved to Italy and began my PhD under the tutelage of Dr. Montecucco in the department of Biomedical Sciences. Even in this institution that was home to many famous scientists such as Galileo and Copernicus, MHC is well known and well respected. Furthermore, Padova was the first university where a woman received a higher academic degree, thus continuing my tradition in institutions that support smart, strong women.

As a student at MHC, I had gained not only the foundations of my academic studies but I had the confidence and poise to approach these people and make valuable connections. My liberal arts foundation made it possible to move into a world where I can work hard during the day and join my friends for dinner by the Grand Canal in Venice, discussing any subject from art to politics.

At MHC, I even learned to scuba dive and now in my spare time, I am part of an Italian Scuba diving group that explores the Venetian Lagoon, beautiful grand lakes of Italy, and the Mediterranean sea off the coast of Historic Roman cities such as Turin, where my college studies of Latin, Ancient cultures and marine biology can come to life.

As a graduate student, my research involves the examination of botulinum and tetanus neurotoxin mechanism of action as well as the entry of these clostridial neurotoxins into nerve terminals as a means to discover fundamental physiological aspects of the synaptic transmission, including the structure of the neuroexocytosis nanomachine.

Furthermore, I am studying the inhibitory prowess of human monoclonal antibodies as a means to obstruct botulinum and tetanus neurotoxin intoxication. Botulinum neurotoxins, produced from different neurotoxigenic bacterial strains of the genus Clostridium, and tetanus neurotoxin, produced from Clostridium tetani, are the most poisonous substances known to humans, with lethal doses in the low ng/kg range.

Consequently, they are included in the category A list of substances of potential bioterrorist use. Botulinum, consisting of seven serotypes (A-G) and many subtypes (>40 molecules in total), causes the neuroparalytic syndrome of botulism, a flaccid paralysis originating in the inhibition of the acetylcholine release at the neuromuscular junctions.

Divergently, tetanus is capable of reaching the spinal cord thus causing the deadly spastic paralysis of tetanus. Despite the opposing symptoms, these two neurotoxins are very similar both from the structural and biochemical point of view. Because of botulinum and tetanus high toxicity, lack of uniform immunization globally, and the use in bioterrorism, it is necessary to create effective and efficacious protection against these toxins.

My work will bring us closer to that goal and I can look forward to a career that I love, allows me to travel and pursue a wide range of interests.