Olke Uhlenbeck

Uhlenbeck is the son of theoretical physicist George Uhlenbeck. He was married to mathematician Karen Uhlenbeck for 11 years (1965-1976).[3] John F. Milligan, a colleague of Uhlenbeck's, said that he appreciated the conversations they had as he developed into a scientist. He also said that Uhlenbeck taught him how to be a leader by showing him what it meant to be engaged in research and how to be intellectually curious. This was said by Milligan after his time working in the Uhlenbeck lab at the CU Boulder.[1]

Uhlenbeck was first published in 1968 at Harvard University for an article titled, “Some Effects on Noncomplementary Bases on the Stability of Helical Complexes of Polyribonucleotides.” The study overviews the conformation of specific polyribonucleotide sequences. The group used synthetic polyribonucleotides with slight distortions and studied whether their conformations stayed in the helical formation or if they took on a new formation. They determined that some of the instability in formation could be due to the non-complementary bases or the bases directly next to those that are non-complementary.[4]

This is a visual representation of a molecule of RNA.

In the 1970’s, he began his work on RNA. Uhlenbeck published many articles on the structure of RNA and its properties. One of his most cited articles is, “The Improved estimation of secondary structure in ribonucleic acids,” published in 1973. This study began a passion for RNA and the majority of his publications thereafter focused on it.[5] He studied RNA binding sites and their synthesis. In 1987, he published another one of his most notable articles in the Oxford University Press. This article is called, “Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates.” They found that transcription occurs at variable initiation sites that can produce small nucleotide strands. These different strands contribute to the variability of RNA. The article has been cited over 2000 times in notable journal articles.  Uhlenbeck and colleagues described a method to make small ribonucleotide sequences that were specific to synthetic DNA used in the study.[6]

He is known for his studies of RNA biochemistry. Some have called him the “Father of RNA.[7]” His most widely accepted publications include those on the enzymatic synthesis of RNA from synthetic DNA. He has also researched RNA polymerases that are involved in the creation of DNA synthesis. He was a leader in the analysis and understanding of the R17 protein coat.[8]  He was initiated into the National Academy of Sciences after his research surrounding the understanding of protein to RNA interactions. Following that research, he along with a group of colleagues defined the accepted model of RNA secondary structure.[1]

In 2015, Uhlenbeck and colleagues studied how to get DNA to form small circles from a library of individual base pairs. The article is titled, "In vitro selection of DNAs with an increased propensity to form small circles." The study found that there was a difference in binding between C/G pairs and A/T pairs. The former tended to disperse evenly, whereas the latter would cluster in groups around DNA. The results indicated that there were different patterns of enrichment between A/T and C/G pairs, as well. The A/T pair pattern was sinusoidal in nature, whereas the C/G pair pattern of enrichment was more moderate with half a helical turn.[9]

Most recently, in 2018, Uhlenbeck published, "Evolutionary tuning impacts the design of bacterial tRNAs for the incorporation of unnatural amino acids by ribosomes." With help from his colleague, Jared Schrader, Uhlenbeck studied the different interactions that tRNA has to compensate for in binding to the ribosome. Each amino acid that is esterfied interacts with the tRNA differently. The implications of this research are very important. They are now able to determine effective ways of incorporating unnatural amino acids into a protein. They are able to do this under lab conditions using bacterial translation systems.[10]

Has published over 200 peer reviewed journal articles, many of which discusses oligoribonucleotides synthesis using the before mentioned synthetic DNA and RNA polymerases. He is called the “Father of RNA” because of his massive contributions to the understanding of RNA structure and associated enzymes, as well as development of synthetic RNA.[7]

In 1993, Uhlenbeck was inducted into the National Academy of Sciences for his work in RNA biochemistry. The National Academy of Sciences is a prestigious scientific community that recognizes outstanding achievements in research and development. Membership is chosen by an elite committee, and only current members can nominate new members.[11]

John Milligan and his wife created the “Olke C. Uhlenbeck Endowed Graduate Fund” which generously funds the tuition of first-year graduate students pursuing their doctorate degrees at the University of Colorado, Boulder. It was named after Uhlenbeck because of the impact he made on the biochemistry department at Colorado. He only joined their staff under the condition that the RNA research groups from all different sectors met regularly. Uhlenbeck knew the value of team interaction, and that one member’s research on different aspects of RNA could contribute to another member of the group’s research.[1]

In 2013, Uhlenbeck was awarded the “Fritz Lipmann Lectureship.” This award is given to someone who has made substantial and influential advancements in biochemistry. He was awarded this due to his research on RNA biochemistry. He and his colleagues were able to determine the aspects that go into the stability of RNA as well as how to synthesize and manipulate it. Many fellow researches applauded Uhlenbeck and said that he was both filled with enthusiasm and support for the biochemistry community. The awards includes a $3,000 prize and funding to present at the Experimental Biology conference in Boston.[7]

He currently runs the Uhlenbeck lab at Northwestern University after having moved it from the University of Colorado. Their current research focuses on the recognition and activity of modified tRNA. One of their major focuses is the development of an aminoacyl tRNA synthetase, which allows the researchers to conduct their experiment when there is excess enzyme in the environment[2]