In this interview performed at Pittcon 2023 in Philadelphia, Pennsylvania, we spoke to Philip Bevilacqua from Pennsylvania State University in regards to the world of RNA chemistry.
Could you please introduce your self and inform us a bit about your present actions?
I’m Phil Bevilacqua, a chemistry, biochemistry, and molecular biology professor at Penn State University. I’m additionally the division head there. My analysis is within the normal space of RNA chemistry and RNA biology.
How has our curiosity in and understanding RNA modified over the previous ten years?
I’ve labored within the area of RNA for over 25 years, from after I was a graduate pupil all the way in which all through my impartial profession. This complete expertise has been tremendous thrilling.
The final ten years, specifically, have seen an actual explosion in our understanding of the significance of RNA and biology from micro RNAs and CRISPR for gene enhancing, each of which have received Nobel Prizes.
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The pandemic was additionally a extremely unbelievable time for RNA because the SARS-CoV-2 virus is an RNA virus, and the vaccines have been made out of mRNA.
What is a tautomer, and the way does it relate to RNA’s chemistry?
There has been an enormous quantity of curiosity recently in modifications to RNA. RNA is a straightforward polymer, similar to DNA. There are solely 4 totally different aspect chains and two sizes: an enormous one in A and G and smaller ones in C and T for DNA or C and U for RNA. They look comparatively comparable, so there may be not a lot molecular variation.
There has additionally been elevated curiosity in covalent modifications to RNA, the place RNA is modified with a methyl group or an acetyl group, and that regulates gene expression.
What we give attention to, nevertheless, are the methods wherein RNA might be noncovalently modified. One instance is tautomers, the place the smallest and the only factor – hydrogen – strikes round as protons or proton switch. While this won’t appear that essential, it’s important as a result of it may possibly change base pairing specificity and refold RNAs.
What are the same old strategies that you’d use to research these RNA tautomers?
There are two broad approaches that we will use to research RNA. One is computational approaches, the place we take a look at submitted databases of RNA buildings, and we analyze these on the pc or do simulations with pressure fields like molecular dynamics and even quantum mechanics. The different method is only experimental, the place we go into the lab and attempt to measure variations.
My lab is primarily experimental, though we do make the most of some computational points. These experiments may take a look at how the bases react with small reactive molecules.
We additionally conduct investigations utilizing various kinds of spectroscopies, similar to electromagnetic radiation. We can get info this fashion, too.
What are the advantages of mixing these computational and moist lab experiments to research RNA tautomerism?
Computational chemistry has come to date during the last 25 years, and about 5 years in the past, the sphere additionally obtained a Nobel Prize in chemistry for the event of computational strategies. This implies that we are actually in a position to examine issues which are extraordinarily troublesome, if not unattainable, to do experimentally.
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Using computational strategies, we will transfer hydrogens round, for instance, to initially decide which of them usually tend to be populated. We can then transfer on to the bodily experiments to look at the way it really seems. This marriage of two strategies finally strengthens our investigations and our investigation outcomes.
What challenges have you ever confronted your self or seen within the area when investigating these RNA molecules?
RNA is just not a very secure molecule, and dealing with it within the lab is at all times difficult. For occasion, enzymes inside a cell, or cell lysates, can degrade the RNA. Therefore, many precautions should be taken when working with RNA to hold out most of these experiments.
Why is it so helpful to broaden our understanding of RNA chemistry, significantly within the context of understanding how organic programs have developed over time?
Basic, curiosity-driven analysis will at all times be actually essential. For instance, understanding how RNA, a easy molecule with simply 4 aspect chains, enhances its range. This info is vital to many sensible issues, similar to human illness, most cancers, and so on., to allow us to higher perceive how RNA may refold and the way that may change gene expression.
It is then essential to contemplate how this may be focused with small molecule therapeutics. Almost all standard medication goal proteins. There are solely only a few that focus on RNA and those who do have a tendency to focus on ribosomal RNA.
Most of the genome is transcribed into RNA however not translated into proteins. However, there’s a huge variety of druggable molecules in RNA, and it might be revolutionary if we might determine how to do this. One of our audio system, Amanda Hargrove, targeted on this explicit facet in her discuss at Pittcon 2023.
What thrilling work are you at present concerned in?
RNA has been a large a part of my profession, and my staff and I try to find out whether or not RNA adopts totally different tautomeric states or charged states that aren’t at all times impartial, so the bases can decide up a proton and grow to be positively charged or drop one and grow to be negatively charged.
What we’ve got developed during the last decade right here at Penn State with numerous colleagues, significantly Sally Assmann within the biology division, are methods to make use of next-generation sequencing applied sciences to research the reactivity of RNA.
Across a complete transcriptome, there could also be tens or lots of of hundreds of thousands of various bases, and we’re utilizing new applied sciences to extend our odds of discovering these uncommon however actually essential states.
What are the advantages of attending face-to-face occasions?
The interactions and connections between individuals are a lot stronger in particular person; this exchanging of concepts and creating of latest collaborations, I really feel, solely occurs when individuals are face-to-face.
What are you most wanting ahead to for Pittcon in San Diego subsequent yr?
One of the thrilling issues about Pittcon is seeing all the brand new applied sciences and instrumentation. I might say in my analysis that it’s about 50% know-how improvement and 50% software to organic issues. Therefore, it’s at all times thrilling to see that facet of issues.
About Philip Bevilacqua
Philip C. Bevilacqua is a Distinguished Professor of Chemistry and of Biochemistry and Molecular Biology at The Pennsylvania State University, the place he’s additionally the pinnacle of the Department of Chemistry. His analysis pursuits give attention to understanding the roles of RNA folding and catalysis in biology. Bevilacqua earned his B.S. in Chemistry with a minor in Physics from John Carroll University in 1987 and his Ph.D. in Physical Chemistry from the University of Rochester in 1993. He accomplished his postdoctoral analysis on the University of Colorado, Boulder, underneath the steering of Professor Thomas R. Cech. Bevilacqua has obtained a number of awards and honors all through his profession, together with the Jane Coffin Childs Postdoctoral Fellowship, the Alfred P. Sloan Foundation Fellowship, the C.I. Noll Award for Excellence in Teaching, and the Penn State Faculty Scholar Medal in Physical Sciences. He can also be a Fellow of the American Association for the Advancement of Science (AAAS) and a Kavli Fellow of the National Academy of Sciences. Bevilacqua has printed extensively, with a complete of 196 publications and an H-index of 51 (Web of Science) and 60 (Google Scholar). He has given 160 invited talks at universities and conferences and co-organized a number of nationwide conferences. Bevilacqua is a member of assorted skilled societies, together with the AAAS, the American Chemical Society, and the RNA Society, the place he serves on the editorial board.
About Pittcon
Pittcon is the world’s largest annual premier convention and exposition on laboratory science. Pittcon attracts greater than 16,000 attendees from business, academia and authorities from over 90 international locations worldwide.
Their mission is to sponsor and maintain academic and charitable actions for the development and good thing about scientific endeavor.
Pittcon’s target market is not only “analytical chemists,” however all laboratory scientists — anybody who identifies, quantifies, analyzes or exams the chemical or organic properties of compounds or molecules, or who manages these laboratory scientists.
Having grown past its roots in analytical chemistry and spectroscopy, Pittcon has developed into an occasion that now additionally serves a various constituency encompassing life sciences, pharmaceutical discovery and QA, meals security, environmental, bioterrorism and different rising markets.