5 Ways to Make ChIP-exo A More Approachable Topic for Students

Introduction: ChIP-exo

Protein and DNA are important macromolecules in the biological system. They play essential roles; both individually and in conjunction with each other. Protein-DNA interactions form the basis of several vital processes like gene expression and regulation, DNA replication, transcription, DNA repair and DNA packaging. 

Proteins interact with DNA in a very defined and specific fashion. Learning about these specificities helps in advancing our understanding about how meticulously the biological world is designed. It has both theoretical and practical importance. This type of interaction studies are carried out using both lab (experimental) and in silico (computational) tools. One such lab tool is ChIP-exo.

It is an immunoprecipitation-based method. Using ChIP-exo one can map the positions and locations on the genome where our proteins of interest are bound. Some of the important proteins studied using this technology are transcription factors, histone modifiers, etc.

Despite immense practical utility, students hesitate to learn about this topic rationally. It sometimes sounds like an extremely sophisticated technology to learn, even though it’s quite simple in its theory and lab handling. Even educators find it difficult to deliver an informative yet captivating lecture on the subject due to several reasons that we discuss below.

Due to the common dilemma amongst most students about how to connect dots between the immunology, cellular biology and genetics concepts as the ChIP-exo works at the interface of all of them, we, at Labster have compiled some resources for you. This article can provide some help as it attempts to identify the major issues encountered by students. It also lists practical solutions teachers and educators can incorporate into their next class. By the end, we’ll convince you why a virtual lab simulation will be helpful not only for your students but also for you as an educator to deliver concepts more efficiently.

Why can ChIP-exo be tricky to teach or learn?

There are 3 reasons why students dread and get confused about the topics of ChIP-exo. Acknowledging these issues is the first step toward making the topic more approachable. 

1. The processes are invisible and thereby sometimes incomprehensible

Since proteins interact with DNA at the molecular level, students often find it difficult to comprehend how and what is going on when ChIP-exo is performed. The idea of DNA shearing, adaptor ligation, exonuclease action, etc, are difficult to follow when taught only theoretically. It also becomes difficult to explain the science behind DNA editing, PCR, immunodetection, sonication, cell lysis, immunoprecipitation, etc as all these techniques manifest their outputs at the microscale that can only be visualized or quantified using assays and not eyes.

2. The technique is content rich and full of details

Dealing with ChIP-exo becomes problematic for students and teachers alike due to an abundance of intricate details from different fields of biology. One needs to be well-versed with the concepts of cellular and molecular biology, genetics, immunology, biochemistry, etc. Explaining to students how ChIP-exo is an advancement over chromatin immunoprecipitation (ChIP) technique that has been in use since 1984 sometimes doesn’t solve the complexity, rather further complicates it. Students also tend to get confused between the different variants of ChIP; simple ChIP, ChIP-exo, ChIP-chip, ChIP-sequencing (ChIP-seq), etc. Remembering the specific details about these different variants and how ChIP-exo differs from these all can sometimes be overwhelming for students. 

3. Requires strong core concepts

In order to make the idea of ChIP-exo clear to students, it is mandatory that educators first work on the basics of the subjects involved. Most of the time, the core concepts and understanding of the basic biology concepts is quite weak which later on creates trouble. Without knowing the importance of basic DNA structure (5’ and 3’ ends), basic protein structure, antibody-antigen reaction, protein-DNA interaction, processes of gene regulation and expression, activity of different enzymes (ligases, exonucleases, nucleases, polymerases), different regular lab techniques (microarrays, PCR, sequencing, sonication), etc can be a problematic situation to be in. 

5 ways to make ChIP-exo more approachable topics to understand

To address the issues encountered while teaching this topic, educators can engage the under-listed solutions in their classes. These can decode many different aspects of ChIP-exo. Not only can they make teaching easier for educators like you but they will also make lessons clearer and easier to assimilate for your students.

1. Emphasize the practical utility of the subjects 

Since the topic is already very heavy on content, teachers should make their students see the practical utility and applications of ChIP-exo in real life. This can serve as the major motivator to passionately associate them with the learning journey. We list a few examples that you can quote in your next class.

• Used to identify transcription factors: Both ChIP-exo and ChIP-seq are used to identify transcription factors that bind along any genome in vivo. 
• Used in both academic research and industry-level assays: Since ChIP-exo produces relatively lower noise than ChIP-seq, it becomes a preferable choice. One is also able to achieve higher near-base pair resolution with ChIP-exo. 
• Used for obtaining structural information: ChIP-exo is also used to obtain structural information of proteins-binding sites of DNA. 
• Used to epigenomic studies: ChIP-exo has proved very useful for studying the epigenetic phenomenon since this technique has a better resolution over its previous versions. It is now widely used to elucidate the specific locations in the genome where specific histone modifications are present and helps one to learn about the role of those histone modifiers. 

Figure: A snippet from ChIP-exo simulation from Labster. It is available for High School and University/College classes.

2. Storytelling can be a way out! 

Since these concepts about genome structure, protein-DNA interactions, and enzyme activities can be quite overwhelming for students, we recommend educators to ease the lessons with small storytelling sessions. Rather than unloading a bagful of information, make each concept sound like a small story where every enzyme, element or factor is a “character” with a defined role as in a “theater play”. 

You can build stories around the underlisted topics to make them easily comprehensible for your students.

• Protein and DNA structure
• Gene expression and regulation (You can also use the Gene Regulation simulation and Gene Expression Unit simulation from Labster)
• Role of different enzymes (nucleases, types of nucleases; endonucleases and exonucleases, ligases, polymerases, proteases, phosphatases, muramidase, N-acetylmuramide glycanhydrolase, T4 DNA polymerase, T4 Polynucleotide kinase, RNase, etc)
• Antibody-antigen reaction and its specificity
• Protein-DNA interaction
• Transcription process and role of transcription factors

Try to build stories around each idea and navigate your students through it. This method of storytelling can help them understand why certain genes are tightly regulated while others aren’t. You can use these Storytelling blogs from Labster as a tool (Blog-1, Blog-2).

Figure: A snippet from ChIP-exo simulation by Labster showing how the experiment works at molecular level. It is available for High School and University/College classes.

3. Amplify the importance of lab handling 

Reiterating all the subtopics when your students are engaged in small planned hands-on experiments is a good idea. We list a number of individualized small experiments that can be planned for high school and university/college students.

• Cell lysis experiments (You can use the Cell Structure simulation from Labster)
• PCR (You can use the PCR simulation from Labster)
• Sequencing (You can use the NGS simulation from Labster)
• Immunological assays and experiments (You can use the Immunology simulation from Labster)

Figure: A snippet from ChIP-exo simulation by Labster showing how the lab handling can be slowly mastered. It is available for High School and University/College classes.

4. Simplify, don’t complicate!

The idea of ChIP-exo can be difficult to understand at first but if simplified properly, it isn’t really difficult to conduct an experiment. The science behind this technique is basic science that does require an investment of time and effort. This is why we can never overemphasize the importance of simple biology concepts. We list a few topics that should be taught with great clarity and objectivity in classes.

• The central dogma of life
• The complexity of gene expression and regulation
• Science behind sonication and cell lysis
• Importance of cell cultures (incubators, ambient temperatures, optical density)
• Different phases of cell growth (log phase, stationary phase)
• Importance of different chemicals and pre-requisites used in ChIP-exo and their roles (magnetic beads, formaldehyde, resin, washing buffers and its types I, II, III and IV, Tris EDTA buffer, Protease K, )

Figure: Magnetic beads used in ChIP-exo. Image Source

• Importance of scientific planning of experiments, variables, controls and replicates [You can use the Experimental Design simulation and The Scientific Method simulation from Labster]. 
• Importance of learning the basic underlying principles of techniques (Sonication, Immunological techniques, NGS, PCR, pipetting, Bioinformatics analysis, etc) [You can use the Immunology simulation,NGS simulation, PCR simulation, Pipetting: Selecting and Using Micropipettes simulation, Pipetting: Master the technique simulation,Bioinformatics simulation  from Labster to teach them.)
• Science behind sticky ends, dA tailing, TOPO cloning, Sanger sequencing and how its different from NGS, etc.s

Figure: TOPO cloning methodology. Image Source

5. Use virtual lab simulations

Since ChIP-exo technique is full of details, we recommend educators and teachers to make the concepts more lucid by using interactive tools and methods. Teachers dealing with these subjects often try various means and methods to do the same. To bridge the gaps that are still left, we have brought the concept of simulations that can make learning a joyful ride for your students. It saves you time assorting resources as the simulations are full of activities, virtual lab experiences, games, and quizzes.

We encourage modern-day educators to make the most of the ChIP-exo simulation from Labster. It takes your students into a virtual world where they can actively engage in the experiments and make full use of the gamification elements to imbibe important concepts. By using this way of active and immersive teaching, our virtual learning platform takes an advent in the field of Science to make the upcoming scientists thorough with the “basics of their respective subjects”. 

You can get in touch to find out how you can start using virtual labs with your students.