Dr. Erik Hartwick

Time is always passing faster or slower than we want, and it is important to keep track of it. Keeping an eye on the clock can be easier or more difficult depending on the situation, and in the case of eukaryotic translation, it needs researchers such as Dr. Erik William Hartwick. Dr. Hartwick is a Postdoctoral Fellow in the Department of Chemistry at Columbia University in Dr. Ruben L. Gonzalez Jr.’s lab where he has been awarded an NIH NRSA F32 training fellowship to focus on time-resolved dynamics of eukaryotic translation. Before joining Columbia University, Dr. Hartwick was a PhD student with Dr. Jeffrey S. Kieft at the University of Colorado Denver, School of Medicine, studying the structured-viral 3’UTR control of protein synthesis.

Dr. Hartwick’s current project is a group effort focused on determining the “conformational dynamics that facilitate regulated steps in eukaryotic translation initiation.” Over a dozen protein factors, called eukaryotic initiation factors, or eIFs for short, facilitate the loading of a ribosomal complex onto an mRNA. Dissecting each factor’s contribution to the assembly of productive translation initiation complexes at the correct start codon is one of the group’s major projects.” He explains his interest in these systems: “While it is important to understand the timing with which each eIF associates to and dissociates from the mRNA and/or ribosomal complex, I find it more important/interesting to determine how the structural dynamics of each mRNA- and/or ribosome-bound eIF contribute to each step of this process in order to facilitate and control ’on-pathway’ initiation.” To do this work, the team has reconstituted eukaryotic translation initiation in vitro. They are currently “performing ensemble biochemical and biophysical experiments in combination with cryogenic electron microscopy (cryo-EM) and single-molecule fluorescence resonance energy transfer (smFRET) studies to tease apart the mechanistic roles that these dynamic aspects of the reaction play in the maturing ribosomal initiation complex. Finally, some of my work uses time-resolved cryo-EM, in collaboration with Dr. Joachim Frank’s group, also at Columbia. The collaboration allows us to use cryo-EM to structurally characterize millisecond-timescale steps that we typically study using smFRET. This approach yields a significant advantage to our studies in that it enables us to solve the three-dimensional structures of short-lived intermediate states that might be identified using smFRET.”

His enthusiasm for the project, the underlying biological questions, and the methodology drew him to his current lab: “I initially met Ruben through his collaboration with the Kieft lab. What initially drew me to Ruben’s group were the types of research and questions his group pursued. They used biophysical measurements, like smFRET, which overlapped with the types of questions I wanted to be able to address in my independent research. My work in Jeff’s group kept funneling me towards more and more quantitative and mechanistic experiments. I understood that I would need more training if I wanted to answer these types of questions. After identifying this gap in my understanding/skillset which I thought was limiting me, I chose Ruben and his group to help me pursue these goals.” Dr. Hartwick enjoys his choice, explaining that if you have yet to meet Ruben, as a mentor he “can be very persuasive, optimistic, and charismatic, which makes conversations exciting and fun. (…) Having a supportive mentor like Ruben is critical for my success right now and I am not sure how or if I can thank him enough for it.” 

“Chase odd results and do the weird experiments. Sometimes you just have to try things out, it is all too easy to convince yourself not to do an experiment.” 

As mentioned above, preceding his current postdoctoral work, he obtained his PhD in another well-known RNA lab: “What drew me to Jeff’s group was the laboratory environment, both socially and professionally, which is one of the best I have experienced, and the lab’s focus geared toward viral RNA mimicry and the co-option of host cellular machinery. As a mentor, Jeff was great because he was supportive and hands-off at the same time.” Among other advice, Dr. Hartwick advises incoming PhD students to “Chase odd results and do the weird experiments. Sometimes you just have to try things out, it is all too easy to convince yourself not to do an experiment.”

Despite chasing ribosomes these days, his favorite RNA is a smaller one: “It might be cliché, but my favorite RNA molecule is likely tRNA. tRNAs are hyper-modified; they can be split in half for different biological functions; they can be repaired; their regulation helps control gene expression in different cellular conditions, such as environmental stress; they can stimulate frameshifting in coding sequences; they are flexible and dynamic, and some are co-opted by viruses to function as primers. I am biased because I worked with tRNA-like structures from plant viruses, but they really are quite versatile and do much more than deliver amino acids to the ribosome.” He also gives honorary shoutouts to his favorite RNA fold (pseudoknot) and favorite non-covalent RNA interaction (base stacking). 

Regarding his favorite RNA journal article, Erik has two answers:

“One favorite RNA Journal article, which is related to my graduate work, was published by Daiki Matsuda and Theo Dreher in 2007 and was titled “Cap- and initiator tRNA-dependent initiation of TYMV polyprotein synthesis by ribosomes: Evaluation of the Trojan horse model for TYMV RNA translation”. The authors largely refute a previously proposed alternative model suggesting that the tRNA-like structure (TLS) of TYMV internally initiates at a specific viral open reading frame (ORF), while simultaneously showing and proposing that the underlying mechanism by which the TLS operates remains elusive. Nonetheless, they show that the mechanism does seem to require ribosomal entry via a 5-cap mechanism and a leaky scanning mechanism, as its two main ORFs are separated by four nucleotides.

A second RNA Journal article that comes to mind is from Dr. Joan Steitz’s group and work from her former postdoc Dr. Jessica Brown focused on the MALAT1 RNA triple helical structure. I was amazed at how cool the structure was and its organization of base triples to maintain a long stretch of triple-helical character. In addition to the structure, I find the model for hiding the 3’-end in order to stabilize the RNA to be a simple and clever solution to resisting RNA turnover and degradation. The article, entitled “Hoogsteen-position pyrimidines promote the stability and function of the MALAT1 RNA triple helix”, focuses on the thermodynamic stability that non-conical base-triples provide MALAT1 triple helix which opens up the sequence variation that other RNAs could employ to form these functional elements.”

While Dr. Hartwick is not on social media, he encourages interested readers to contact him via email. You might also catch him at the Columbia RNA Salon or RNA Society meetings!