The Science Behind the Image Contest Winners: Group II Intron Ribozyme

The BPS Art of Science Image Contest took place again this year, during the 61st Annual Meeting in New Orleans. The winning image was submitted by Giulia Palermo, a postdoctoral fellow in the group of J. Andrew McCammon at the University of California, San Diego. A team of three scientists composed the image:  Giulia Palermo created the original design, Amelia Palermo (ETH, Zurich) made the handmade painting, and Lorenzo Casalino (SISSA, Trieste) performed digital manipulation on the picture. Giulia Palermo took some time to provide information about the image and the science it represents.

palermo-giulia-61-70469-2

With this picture we would like to send as the main message that Physics and Art try to interpret the beauty of Nature in different ways but there is a natural overlap between these disciplines, which could lead to wonderful discoveries and amazing beauty.

Group II intron ribozyme perform self-splicing reactions. In the picture, two scissors are used to represent this mechanism. What we like about this image is how a handmade painting could capture the fundamental aspects of the mechanistic action of the system. Besides the beauty of handmade painting, we enjoyed our teamwork and, fostered by the passion for this research, we have been motivated to submit this image to the Art of Science Image Contest.

This image has been inspired by the work we have done in the group of Prof. Alessandra Magistrato (SISSA, Trieste), in collaboration with Prof. Ursula Rothlisberger (EPFL), which resulted in the publication of our research in the Journal of American Chemical Society and in the Journal of Chemical Theory and Computation, while other equally exciting results are in preparation for publication. Below, we report details of our publications:

  1. Casalino, G. Palermo, U. Rothlisberger and A. Magistrato. Who Activates the Nucleophile in Ribozyme Catalysis? An Answer from the Splicing Mechanism of Group II Introns. J. Am. Chem. Soc. 2016, 138, 1034.
  1. Casalino, G. Palermo, N. Abdurakhmonova, U. Rothlisberger and A. Magistrato. Development of Site-specific Mg-RNA Force Field Parameters: A Dream or Reality? Guidelines from Combined Molecular Dynamics and Quantum Mechanics Simulations. J. Chem. Theory Comput. 2017, 13, 340–352.

My research exploits advanced computational methods – based on classical and quantum molecular dynamics (MD), novel cryo-electron microscopy (cryo-EM) refinement – and their integration with experiments to unravel the function and improve biological applications of key protein/nucleic acids complexes directly responsible for gene regulation, with important therapeutic applications for cancer treatment and genetic diseases. As a next-generation computational biophysicist, I aim at going beyond the current limits of time scale and system size of biomolecular simulations, unraveling the function of increasingly realistic biological systems of extreme biological importance, contributing in their applications for effective translational research.

The World Health Organization reported that ~8.2 million citizens die each year for cancer, while genetic diseases affect millions of people. As such, the clarification of the fundamental mechanisms responsible of gene expression and of their therapeutic implications is of key urgency to society.  By using advanced computational methods and by their integration with experiments, I seek to unravel the function and improve applications of biological systems of extreme importance. My current interest – as a post-doc in McCammon’s lab at UCSD – is in the clarification of the mechanistic function of the CRISPR-Cas9 system via computational methods. Additionally, I am interested in long non-coding RNA, which regulates gene expression, and in intriguing protein/DNA systems, whose mechanistic function is at the basis of genetic inheritance.

BPS Summer Program Alumni Spotlight: Joshua Mannheimer

Josh_Mannheimer_PhotoWe recently had a chance to interview Joshua Mannheimer, an alumnus of the 2013 Biophysical Society Summer Program in Biophysics, and learn about what he has been up to since his time in the Summer Program. Currently, Joshua is at Colorado State University wrapping up his Master of Engineering Degree in mechanical engineering after which he will be directly matriculating into the Biomedical Engineering PhD program.

What is your research focus?

I consider myself an applied computational biophysicist. My goal is to use computational tools to guide experimental scientists by providing insight into biological processes through modeling. Additionally, I am interested in developing computational tools to assist in clinical medicine. My current project uses advanced statistical techniques, called machine learning, to predict the efficacy of chemotherapeutic agents on certain cancer types based on genetic analysis.

When and how did you first become interested in this type of research?

I really got interested in biology in high school, but after taking physics my senior year I decided to get my BS in physics. After a couple years of pursuing physics I had decided to take a few chemical and biological engineering courses; it was through these courses I was connected with a faculty member in the Biomedical Engineering department who happened to have a background in physics. It was through him that I realized the potential to use physics-based models to probe questions in biology.

In terms of what I do right now, it was actually quite serendipitous. After my first year in the ME program I was looking for an internship in industry to build experience professionally. After this did not work out, I needed to do something for the summer. I contacted a faculty member in the Biomedical Engineering department who happened to need someone experienced with programming. This is how I learned about big data and machine learning and was immediately aware of how big of an impact this could have on clinical medicine.

Have mentors played a role in your success?

I have been fortunate enough to have many mentors play a role in my life from school teachers who fostered my curiosity, many adults whom I looked up to as a kid who always encouraged me, and of course some of the faculty I have worked for over the years who invested time in my development as a scientist. Most importantly I have always had a supportive family.

What have been some of your toughest challenges so far in advancing your career?

I was diagnosed with Obsessive Compulsive Disorder (OCD) early in my childhood and that has by far been the biggest obstacle I have faced growing up. It impacts the way I learn and work when it comes directly to academic pursuits; however, managing my mental health while in a demanding program has been the biggest challenge, one I still struggle with but which makes me even more determined to succeed.

What was the most important thing you learned or took away from the summer program that helped you get to where you are at now?

I participated in the summer program right after I had graduated with my BS. At that point I had felt a little dismayed because I had just finished this really demanding degree and I still felt like I knew nothing. During the summer course I realized that what I really learned was how to solve problems and was impressed with how I could implement these skills to work on novel problems. It really put things into perspective.

What was your favorite thing about the summer program?

I really enjoyed the people. It was really beneficial to work with people who came from different academic backgrounds but more importantly to meet new people from different backgrounds and places.

What advice would you give for current undergraduates interested in pursuing a higher degree?

I would encourage any student to research the opportunities a graduate degree affords them and how that degree, and more importantly that research area, will lead to employment opportunities in industry and academia. After all, a degree is not useful unless you can use it.