Working with Tom Maniatis

I felt blessed. I felt that the chance to go to Harvard and to work in a lab that had all the technology that I needed was amazing. It was a godsend. I felt so privileged and grateful. So, I got on the plane and went to Cambridge and Wally Gilbert had been, and Tom Maniatis, and various people were purifying restriction enzymes. Tom Maniatis was the person who actually trained me, he was phenomenal.

Lambda Repressor Transcript

They made their own restriction fragments and restriction enzymes, and there was a perfect restriction fragment that had both promoter PR, which was in control of lytic growth, and the PRM promoter, we thought, that was in control in lambda repressor, but no one had mapped the promoter for lambda repressor. And so, we didn't even know where it was. We didn't even know if it was actually on this fragment. But with my polymerase prep and with their repressor and with the restriction fragments that Tom Maniatis made, I put polymerase in my test tube with appropriate nucleotides and radioactivity, and at low concentrations of polymerase, I could see the PR promoter. I also, because Mike Chamberlain had taught me about salt concentrations, he taught me that salt was really important for the activity of polymerase and be careful not to use too much salt. So, in those times, people were using extremely high salt concentrations to do transcription, but I remembered what Mike Chamberlain told me. So, I used a much lower concentration and I dumped polymerase repressor in and polymerase. And miraculously, within the first two weeks, I saw the PR promoter being turned off and simultaneously I found this new transcript being turned on. And I thought, oh my God, this must be the repressor transcript, and there it was. The experiment that was going to be too hard for me to ever do, in the first two weeks as a visiting student, I suddenly had a gel that looked like I might actually have the lambda repressor transcript.

Sequencing the Lambda Repressor Transcript

Oh, many times, many times. And you know, who is going to believe it? And so, eventually, what I had to do was sequence the transcript and show that it actually was lambda repressor, and there were various tricks we used to show how it was being transcribed. But the bottom line was that I had an in vitro assay, in vitro transcription assay, thanks to the work in Mark Ptashne's lab and the brilliant people, and thanks to Wally Gilbert who knew how to sequence and make everything. And so, within a very short time, it was clear that project I really wanted to work on was going to be doable. And so, I worked really hard at it, but I had been away from Berkeley then for many months.

Dr. Barbara Meyer is a genetics, genomics and development professor in the molecular and cell biology department at University of California, Berkeley. She also serves as an adjunct professor in the biochemistry and biophysics department at University of California, San Francisco’s School of Medicine and an HHMI investigator. Dr. Meyer completed her undergraduate studies at Stanford University and began her PhD at the University of California, Berkeley and finished at Harvard University. During her post-doctoral work, she researched how chromosomes determined sex of C. elegans at the Cambridge University Laboratory of Molecular Biology with Dr. Sydney Brenner.

Dr. Meyer received her Bachelor of Arts in Biology from Stanford University in 1971, her Master of Science in Molecular Biology from the University of California-Berkeley in 1975, and her PhD in Biochemistry and Molecular Biology from Harvard University in 1979. She then began post-doctoral research at the MRC Laboratory of Molecular Biology to research how chromosomes determined sex of C. elegans. After completing her work at the MRC, she established her first lab at MIT to further analyze sex determination mechanisms.

Dr. Meyer was a tenured professor at MIT until 1990 where she became a genetics, genomics, and development professor at the University of California-Berkeley. In 1995, she became a member of the American Association of Cell Biology and American Academy of Arts and Sciences. She also became an investigator for the Howard Hughes Medical Institute in 1997, where she and her lab successfully identified the master gene involved in sex determination. This breakthrough has helped advance research on chromosome repression and X chromosome dosage compensation.

Dr. Meyer has received many awards for her work, including the Genetics Society of America Medal in 2010, the Francis Amory Prize in Medicine and Physiology by the American Academy of Arts and Science in 2017, the E.B. Wilson Medal by the American Society for Cell Biology’s highest honor for science, the Thomas Hunt Morgan Medal, and was also elected to the National Academy of Medicine all in 2018.