May 4, 1995

Dr. Lawrence P. Wennogle
CIBA Pharmaceuticals Division
556 Morris Avenue
Summit, NJ 07901

Dear Search Committee:

 I am writing this letter in support of Anton Yuryev’s application to do advanced research work in your laboratory.  Yuryev is talented and creative scientist who is one of the most independent students I have ever known in our graduate program.  As you may know, Yuryev was among the first members of Jeff Corden’s lab to venture into the yeast system, and because I am a yeast geneticist and because initially, my lab was on the same floor as Corden’s, I served as a kind of informal advisor for Yuryev’s work.  I still remember the intensity of my first meeting with Yuryev; despite the fact that he was not yet well versed in yeast genetics, he was absolutely chomping at the bit to get the first experiments done; this man has incredible drive and perseverance.  The down side of this is that, because he does so much work independently, he does sometimes end up learning things the hard way.

 Yuryev worked on two projects with which I am familiar, the isolation of extragenic suppressor mutations that suppress amino acid substitution mutations in the repeated C-terminal domain of RNA Pol II, and the isolation of CTD binding factors via the two-hybrid system.  These projects form the basis of his Ph.D. thesis.

 The extragenic suppressor project resulted in the cloning of a novel gene called SCA1, and the discovery that mutations in this gene (and occasionally other mutations as well) result in suppression of mutations at one position in the CTD repeat, but not at a second position.  As these positions represent sites of phosphorylation this is a most interesting result. What may not be clear from the write-up of this work is the absolutely nightmarishly complicated genetics he got into in this project, and he has tried mightily to clear this up but his own data indicates that some of the original mutants he studied were multiple mutants and hence, much more difficult to sort out.  Also, the extremely slow growth of the suppressed mutants made the analysis extremely time consuming.  That he stuck with this project as long as he did is a testament to hi tenacity.

 Yuryev’s second project was much more successful, and suggested a new function for the CTD, namely interaction with RNA processing factors.  If these findings hold up, they would provide an important new insight into the possibility that transcription and RNA processing are coupled.  Yuryev found that, unlike other CTDs and CTD regions, a particular region of the mouse CTD would not activate reporter gene transcription when fused to GAL4 DNA-binding domain (several other groups had tried this and given up).  He then used this as bait in a two-hybrid screen, and turned up a number of interesting cDNAs encoding proteins in the SR family.  He was also able to map the CTD-interacting domains in these proteins.

All in all, Yuryev’s drive, capacity for hard work, ability to master complex systems and raw brainpower are among the better graduate students in the School of Medicine.  Yuryev has excellent potential as a research scientist.