HUIT Supports Cutting-Edge Bioinformatics Research Tools in a Freshman Seminar

January 9, 2017
Nanopore Sequencing
Nanopore-based DNA sequencing concepts generally entail one of the DNA strands passing through the nanopore sensor, where the individual nucleotides (DNA building blocks) are distinguished from each other. Credit: Jonathan Bailey, NHGRI.

By Daniel Jamous, Senior Instructional Technologist, Academic Technology for FAS 
In Fall 2016, two HUIT groups – Academic Technology for FAS and the division of IT Support Services responsible for managing Harvard’s computer classrooms – collaborated to provide students with in-class access to cutting-edge bioinformatics research tools. The course, called Freshman Seminar 25o: Building a Living Cell One Brick at a Time and taught by Senior Lecturer Alain Viel from the Department of Molecular and Cellular Biology, allowed students to conduct an experiment in the nanopore sequencing of bacteria present in Kimchi, the fermented Korean dish. Because of the resource-intensive nature of the bioinformatics software used for nanopore sequencing, and because of the need to ensure each student was working in the same virtual environment, a computer classroom was utilized for this portion of the course.

Viel proposed his Freshman Seminar for the first time in the Fall of 2012, after seeing how many freshmen were interested in his research-based course Life Sciences 100: Experimental Research in the Life Sciences. Although there are no prerequisites, each offering of the freshman seminar is capped at 14 students, who are chosen from 80 to 90 applicants based on interest level, essays, and on Viel’s desire to include students with diverse levels of experience in biology. The course is hands-on and laboratory-based, usually centering on teaching students how to design and conduct experiments into how synthetic biological systems are built. Teams of students have access to a fully equipped laboratory dedicated to undergraduate research during the weekly 3-hour laboratory sessions.

Due to recent advances in nanopore technology, a novel technique for probing and sequencing individual DNA molecules that was spearheaded by Harvard Professor (Emeritus) Daniel Branton and UC Santa Cruz Professor Dave Deamer, Viel decided to shift the focus of the Fall 2016 iteration of his Freshman Seminar, and to introduce students to the inner workings of nanopore sequencing. With the help of Physics graduate student Teaching Fellow Stephen Fleming, students spent the first part of the semester learning the basic principles behind nanopore sequencing. Encompassing concepts and techniques from both physics and biology, students performed a combination of “dry” and “wet” experiments such as making electrodes, measuring ionic currents, creating a lipid membrane and isolating bacteria from food. Students worked with Kimchi, the traditional Korean dish composed of fermented cabbage, to analyze the bacteria responsible for the fermentation. Because nanopore sequencing is an ultra-high speed method for sequencing DNA, a computer is necessary to analyze the voluminous amount of data generated through this technique. For the first time in this course’s history, students were offered the opportunity to analyze their own data through the use of bioinformatics software tools, with the ultimate prospect of determining the sequence of the genome of the bacteria responsible for the fermentation of their Kimchi extract samples.  

The November 2nd and 9th class meetings were dedicated to training the students on using bioinformatics tools to perform sequence alignment, assembly, data analysis, and visualization. These sessions were led by Miten Jain, a graduate student in the nanopore group at UC Santa Cruz, where the sequence alignment package marginAlign and other bioinformatics tools were developed. Because marginAlign is run from the command line and is resource-intensive due to the amount of data being analyzed, and because installing and running these bioinformatic tools in the heterogeneous environments of student laptops could have introduced unnecessary technical challenges and distracted both students and instructors from the course’s pedagogical goals, the teaching staff decided to use a HUIT computer classroom (namely Northwest Labs B-127) for the training sessions. With guidance from Jain and coordination from Senior Instructional Technologist Daniel Jamous, Louis Alix-Garth’s team from IT Support Services installed the open-source bioinformatics software and supported its successful use in the seminar. Students were also afforded access to the computer lab to work outside of scheduled class time, and were able to write final reports on their own data as part of the course Pass/Fail credit. The software will remain available in the computer lab for the rest of the 2016-17 academic year so that students who might choose to further their research experience (for example, through Independent Study) will have the option to do so.

Through state-of-the-art research lab experiments, techniques, and software tools, and because of the successful collaboration between these HUIT units and FAS faculty, these students have been exposed to the exciting and emerging multi-disciplinary field of synthetic biology, a unique experience not easily reproducible. Says Viel: “Very few people can say at the end of the fall of my Freshman year, ‘I had the possibility to sequence the genome of a bacteria.’”