Nikolaus Trautmann

Home Institution
Albert-Ludwigs-Universität Freiburg

Host Institution
University of California, San Francisco
Mentor: Matthew M. La Vail

E-Mail
picknick@bigfoot.de

Research Topic
see Abstract
Personal Reactions to the U.S. Experience
To be honest, for various reasons, the United States overall is not my favorite country. But…wow! San Francisco is certainly one of the best places to be in the world. The city is great, interesting, freaked-out and absolutely not typically American. The climate is perfect, not too hot, not too cold (if you can live with the fog), and California offers everything from mountains for skiing and hiking, to the ocean for surfing. I've started rock-climbing and mountain-biking, among other things, which I always wanted to do, but never found the time for before. Traveling is another nice aspect. I've visited many other BMEP students and friends in very different parts of the United States.
Greatest Difficulties Encountered
Finding social contacts was a lot tougher than I had expected. The people in my lab were all great but not of the sort to go out at night. My first roommate was terribly boring and most Americans I met were very busy with their existing friends and hobbies. UCSF is a small university without undergraduates, and there aren't many other exchange students either, so it was hard in the beginning. However, after a little while things were much better.
Most humorous incident
After returning to San Francisco, after Christmas, Roman and I went to a bar, and I showed him the new 20 Euro bill. The bartender got interested and wanted to have a look, too. Soon my bill was passed around the whole bar, and people were discussing the safety features and comparing it with a $20 bill. Just before we left, a guy approached me and asked if I could show him some new EURO coins, too. It was very amusing.

Helpful Hints for Future Students
- Come to San Francisco. Seriously: picking a great location can make up for eventual bad luck in the lab.
- Get yourself a Social Security card as soon as possible. A local driver's license can also be a very valuable thing. Be prepared for terrible bureaucracy everywhere.
- Life is expensive in the US, and especially in San Francisco. But usually it's possible to get financial support from your lab here; don't be afraid to ask.
- Get a bank account at Bank of America; it is a member of the German cash group. I had an account at the Deutsche Bank and could withdraw cash for free. However I heard with Commerzbank it doesn't work as well.
- Explore a number of different labs before choosing. Try to communicate as well as possible with your new lab group and be clear about your and their objectives, and your projects in the lab. Bigger labs may offer more contacts and more methods to learn, but smaller ones (like mine) may have a more personal atmosphere.
- Be open to the American culture. Don't try to continue your life the way you used to have it. Try watching American football, eating American food, going to parties that start at 5 p.m. or small-talking all day. You'll get back to your old lifestyle soon enough.
- Consider taking two semesters off, it may be worth it.

September 11
Fear. Anger. Nausea. Frustration. Confusion. Disbelief. Grief. Detachment. Numbness. Sorrow. Loss. Surrealism. Denial. Exhaustion. Ambiguity. Apathy. Idealism. Cynicism. Loss of control. Disconnection. Victimization. Hypocrisy. -- The space here is insufficient to elaborate my thoughts and feeling after the terrorist attacks, but, to cut it short, it was tough to be in Boston when it happened, but tougher to be in the United States during the post-9/11 events.

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Abstract on Research Topic:
Rhodopsin levels in eight rodent models for retinal degeneration
Authors:
N. Trautmann, M. La Vail
Institution at which research was done:
Department of Ophthalmology, University of California, San Francisco.
Purpose:
Photoreceptor degeneration is the cause of blindness in diseases like retinitis pigmentosa, which affects 1 in 3500 people worldwide and age-related macular degeneration, which affects vision in the elderly in as many as 1:3 by the age of 75. Several rodent models have been established to study new treatments for these diseases.
The MER protein plays a crucial role in phagocytotis of apoptotic cells. Mice with a mutation in the kinase domain of the Mer gene, show, besides an immune deficit, a form of photoreceptor degeneration. Due to the inability of the RPE (retinal pigment epithelium) to phagocytose discs of rod outer segments, they form a debris zone in the outer retina, which causes photoreceptor cell death. P23H and S334ter are two common mutations in the rhodopsin protein responsible for retinitis pigmentosa that can now be studied in a rat model. Seven different lines of transgenic animals are currently being characterized to serve as models for human retinal degeneration. Besides functional studies with ERG (electroretinogramm) and structural analysis, the levels of rhodopsin in the eyes of these animals will offer another parameter to characterize degeneration and measure the success of future therapies.

Materials and Methods:
Animals were dark-adapted overnight and all procedures performed in dim red light. Both eyes from each dark-adapted animal were pooled after lens-removal and homogenized in 0.85 ml 20mM MOPS containing 1.5% lauryl maltoside and 0.2 M hydroxylamine hydrochloride. The homogenate was extracted on ice for 3h and centrifuged for 15 min at 135.000 xG at rmax in a Beckman TL100 centrifuge. The change in absorbance at 498 nm was measured with a Spectronics Genesys 5 after bleaching (60s at 10 cm with a 60W bulb) and used to calculate the content of rhodopsin per eye. (Absorbance coefficient of rhodopsin at 498 nm = 42 000 M-1 cm-1 )

Results:
MerKD. At postnatal day (P) 25 the knock-out animals contained 67.3% (p<0.01) more rhodopsin than control animals. These levels drop to almost normal at P40 (+14.7% p=0.3) and by P60 there is hardly any rhodopsin left in the retina (-96.8% p<0.05)
P23H. The Rhdopsin levels in all three lines of P23H mutants corresponded very well with previous structural and functional levels of these animals: P23H-1 rats have 57.8% normal at P15 and15.3% at P30. P23H-2 animals contain 71.8% (P60) and 40.5% (P120) compared to normal and P23H-3 rats have 54.7% at P30 and 44.5% normal at P90.
S334. Line 3 (S334-3) animals contain only 3.5% rhodopsin compared to control animals at P15, while S334-4 animals have a slower time course: 58.0% at P30, 30.1% at P60 and 15.9% at P120. S334-5 rats have only 7.4% rhodopsin compared to control animals at P30. Line 7 mutants show a rapid degeneration, their rhodoopsin levels are down to 60.4% at P15 and 14.4% at P12. S334-9 animals have almost normal rhodopsin levels at P30 and P90.
Conclusion:
The fact that rhodopsin levels increase first in the MerKD animals before degeneration begins corresponds well with the thickness of the outer segment layer, and is a result of the phagocytosis defect in these animals. Our results are very similar to observations made in the RCS (Royal College of Surgeons) rat, an inbred rat model with a similar Mer-mutation. The levels of rhodopsin in most of the P23H and S334 lines mirror results we have obtained from structural analysis (outer nuclear layer thickness and rod outer segment length) as well as ERGs performed on these animals.
S334-9 animals have shown an early onset functional retinal deficit in contrast to normal structural properties. These results here now show that this deficit is not due to a lack of functioning rhodopsin. Having described the characteristics of retinal degeneration in 8 different animal models now offers a number of approaches for future therapies.

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