In mid-May, I embarked on my last undergraduate adventure -- traveling to
Helsinki, Finland for a two month BRAVO! research experience in the laboratory of
Dr. Elina Ikonen in the Department of Biochemistry, at the National Public Health
My trip began with my flight being cancelled from Tucson to Dulles. Luckily,
troubled United Airlines was able to put me on an earlier flight, and away I went
into the friendly skies. My favorite part of international flights, besides the
numerous meals, is the in-flight progress map that appears every now and then to
show what area of the earth the plane is over. From Frankfurt, I boarded a
Lufthansa flight to Helsinki. A little over an hour later, the Finnish
archipelago came into sight 30,000 feet below. Upon seeing this, a sensation
went through me, my adventure had begun! Helsinki is a city situated around a
vast forest of birch trees and ferns. In Helsinki, if is not a building, it is
green! After I met Titta, a Ph.D. student from my new lab, and settled into my
apartment, we rode a tram to the laboratory, which was larger than I expected and
was used to. However, there were three separate research teams working there.
I began work immediately (that is after arriving a few hours late because I got
lost riding my borrowed bike). Helsinki's vast forest is full of mountain bike
trails and one wrong turn can lead a bicyclist to St. Petersburg. Luckily, my
new colleagues were amused, and I did not leave a bad impression in their minds
My project was a continuation of the Niemann Pick type-C (NPC) research I was
involved in with Dr. Robert Erickson, Pediatrics Department at the Arizona Health
Science Center/Childrens' Research Center. NPC is a genetic disorder that is
fatal in all of the children afflicted. This disorder is characterized by the
accumulation of unesterified cholesterol in the liver and spleen. However,
little is known regarding the fatal, neurological complications that develop.
The NPC1 gene was cloned in 1997 and extensive research began to unravel the
mysteries behind the NPC protein's topology and its role in cholesterol
My primary goal in Helsinki was to determine what mutations on the NPC alleles of
a late Finnish patient with NPC caused the loss of function in the protein. From
the patient's pedigree, it was known that his inherited NPC gene included a point
mutation from his father as well as a four-nucleotide deletion from his mother.
A third mutation -- a point mutation not present in either of his parents also
existed. In order to determine the mutations responsible for the NPC disorder in
this patient, I transfected multiple different cell types, all containing
indigenous non-functional npc protein with npc protein containing only one of the
Once the transfections were done, I co-stained all of the transfected cells with
filipin and florescent antibody specific for the npc protein. Filipin is a
florescent molecule, which binds with a high affinity to unesterified
cholesterol, the type of cholesterol that is found in excess in many of all NPC
patients' cell types. The antibody stain was done to determine the cells that
had been successfully transfected; they appear brighter than the other cells
because they contain more npc protein. Normally, any of the cells containing
loss-of-function npc protein will show an intense filipin staining, but if they
are transfected with a NPC DNA that, when eventually translated, introduces a new
npc protein that functions properly, the unesterified cholesterol will be
processed correctly and there will be little filipin staining. In other words,
transfecting cells that originally have nonfunctional NPC DNA, with functional
NPC DNA should correct the cholesterol storage. This was the general idea behind
all of the different transfections I did, to see which of the mutated NPC DNA's,
if any, decreased the amount unsterified and likewise amount of filipin staining.
Unfortunately, the only transfection that displayed a correction in cholesterol
metabolism was the transfection with wild-type NPC DNA, as would be expected. My
main conclusion, therefore, was that all of the patient's mutations caused a loss
of function in his npc protein.
My experience in Finland was one of the best in my life, and I was able to learn
a lot of science in a very short time, plus live in a foreign country. The
Finnish language has no ties to English; it is believed to be derived from
Mongolian peoples. The Finnish people are unique. They are quiet -- considered
to be the most reserved among all Europeans. They do not say things such as
"excuse me" and "I am sorry," so when you get bumped into do not expect an
apology. They are not being rude; on the contrary, they are very nice people.
They are best known for three things: Nokia phones, Mika Hakkinen (this year's
leading formula one driver), and saunas (which I, but not my swimming suit),
experienced in the "natural" Finnish way.
It took a while for my brain to become accustomed to 22-hour hours of daylight.
I had the wonderful opportunity to travel north to Lapland, where, on June 24,
I saw the full sun at midnight!
There are many people to thank for my adventure, including a special thanks to
Carol Bender, Dr. Erickson and Dr. Ikonen. BRAVO! is a great program, and in
retrospect, two months was way too short.
Peter Carbone, UBRP alum from Dr. Erickson's lab, Pediatrics