Two Generations of TSRI Graduates
By Jason Socrates Bardi
When Assistant Professor Ben Cravatt places the hood over
the head of Matthew Patricelli and hands Patricelli his diploma
at this years graduation ceremony, three milestones
will be passed.
For Patricelli, the ceremony is the culmination of the work
he started nearly five years ago when he came to The Scripps
Research Institute (TSRI) from McGill University.
For Cravatt, this moment will be a special one because Patricelli
is his first student.
And for the institute, the event is a first as well, because
Cravatt is the first alumnus of TSRIs graduate program
to guide another student to completion of the program.
Cravatt came to TSRI in the early 1990s after completing
his undergraduate degree at Stanford University. When Patricelli
came to TSRI in 1996, Cravatt was finishing his Ph.D. under
the guidance of Professor Dale Boger, Vice President for Academic
Affairs and Dean of Graduate Studies Norton Gilula, and President
Richard Lerner. Patricellis research arose out of the
last phase of Cravatts dissertation.
As a graduate student, I was working on identifying
proteins associated with the fatty acid amide oleamide,
says Cravatt. Oleamide is a neurologically active molecule
that appears in the cerebrospinal fluid of tired mammals.
The last part of Cravatts thesis was characterizing
how oleamide works. "But that was hard work without genes,"
says Cravatt. "I wanted to find enzymes associated with oleamide
and get their associated genes and manipulate the system that
way. Thats how we got fatty acid amide hydrolase (FAAH)."
FAAH is a 587-amino acid membrane-bound enzyme that breaks
down small molecules like oleamide. It belongs to a large
group of serine hydrolases, a class of enzymes containing
active site serine residues that catalyze the hydrolysis of
specific substrate molecules. These enzymes arose very early
in evolution and are ubiquitous in naturefound even
in the earliest single-celled organisms.
When Patricelli started working with Cravatt, he was simply
characterizing FAAH as a small project, but the study quickly
turned into full-fledged thesis research.
"When I started working on the project, Ben was still a
grad student but just for a few months," says Patricelli.
"I got here in August, he defended in October, and then we
started the lab in January ."
Significantly, Patricelli found that FAAH has an unusual
mechanism. Almost all mammalian serine hydrolases cleave their
substrates through a reaction involving a Ser HisAsp
active site catalytic triad, but FAAH uses a LysSer
Patricellis dissertation, titled Biochemical and
Physiological Investigations of Fatty Acid Amide Hydrolase,
incorporates everything from his early expression and
purification of FAAH to its mutagenesis and the results of
comparative kinetic and in vivo studies.
"He reminds me of myself in many ways," says Cravatt. "Hes
very excited about science, and he likes to think of the intricacies
of what hes doing and develop hypotheses, but at the
same time hes not so attached to his hypotheses that
if his data tell him otherwise, he isn't willing to dump the
original hypotheses and start anew."
"I'm definitely very proud of him and will miss him greatly,"