Patananan, Alexander N.

Alexander is a second year trainee and is in the Department of Chemistry and Biochemistry.  His research mentor is Dr. Steven Clarke.  He received a B.S. degree in 2008 from UCLA.

Mentor: Dr. Steven Clarke

Research project:

As organisms age, proteins can spontaneously accumulate covalent damage to become non-functional, or even toxic.  The success of organisms may therefore depend on their ability to first identify damaged proteins, and then to either repair or remove these species before they build-up to detrimental levels.  L-isoaspartyl O-methyltransferase (PCMT1) is an important enzyme involved in this protein repair.  Although approximately 100 days after birth PCMT1 knockout mice plateau in accumulated cellular/tissue isoaspartyl-damaged proteins, subsequent increased levels of damaged urinary peptides and death by massive seizures occur. I will use high-performance liquid chromatography and electron capture dissociation mass spectrometry to detect these abnormal urinary peptides in PCMT1 knockout mice and determine which proteins and tissues are most susceptible to damage.  Specific inhibitors and activation markers for autophagic and proteasome pathways in various tissues of these mice will be used to determine if known proteolytic systems and/or novel L-isoaspartyl specific degradation pathways are activated. In addition to investigating isoaspartyl damage in a mouse model, biochemical techniques will be employed to elucidate how Saccharomyces cerevisiae, an organism maintaining low isoaspartyl damage and no PCMT activity,handlesprotein damage.