What four building blocks can do: the challenge of understanding and exploiting nucleic acids.

​Abstract

I like to lecture from a historical perspective. Much of the work we do relates to the central dogma of biochemistry, which found its origin in the structure of the double stranded DNA helix described by Watson and Crick in 1953. I intend to cover a lot of topics, but they are all centered on my love for nucleic acids: How they work and how you can use them. Our laboratory has a legacy in NMR structural biology and tailor-made synthesis of isotope labeled RNA and DNA. I will start with providing a brief overview of the nucleotide and nucleic acid synthesis schemes available for analytical and material sciences. I will show how these can be used for studying mechanistic aspects the transcription - translation machinery, after which I will dive into a key scientific question: how molecular crowding affects molecular interaction and kinetics in cellular environments. The last part of my talk will focus on DNA aptamers. Aptamers are artificial RNA or DNA oligonucleotides with specific structures and functionalities that can be selected from large oligonucleotide libraries using a procedure called in vitro SELEX and rival antibodies in affinity and selectivity. Using our DNA technology as framework I will discuss how we can devise and apply multivalent aptamer strategies for bionanosensing and in achieving cellular regulation from the outside in.

Bio 

Hans Heus was born on August 3 1957 in the tiny village Schermerhorn in the province North-Holland, The Netherlands. He spent most of his youth in the residence The Hague, where he graduated from high school in 1976. He studied chemistry at Leiden University from 1976 - 1982 and graduated with a major in biochemistry and a minor in physical chemistry. For his minor he went to the University of Regensburg (Germany) from September 1981 - April 1982 to the laboratory of professor Hans-Jürgen Hinz. He started his PhD study in 1982 under the supervision of professor Peter H. van Knippenberg, and received his doctoral degree in 1987 on the thesis “The 3'-terminal colicin fragment of 16S ribosomal RNA, biochemical and biophysical studies". Being exposed to the possibilities of NMR spectroscopy in structural studies of nucleic acids in the then Dutch national NMR facility in Nijmegen, supervised by professor C.W. Hilbers, he decided to deepen his understanding in NMR structural biology and moved to the university of Boulder at Colorado, where he was a post-doctoral fellow under the supervision of professor Arthur Pardi from 1987 - 1990. He moved back to Nijmegen to the laboratory of Biophysical Chemistry of professor Hilbers in 1991 where he has been ever since, first as a KNAW fellow and became assistant professor in 1996. His research interests are in structure-dynamics and applications of nucleic acids for which he uses a broad multidisciplinary approach, covering molecular and chemical biology tools to prepare tailor-made samples and various advanced spectroscopic techniques to characterize biophysical properties. Recently the focus is on the influence of molecular crowding on the transcription-translation machinery, functional non-coding RNAs and multivalent aptamer technology in bionanosensing and cellular regulation.​