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Cryo-Em brings a wealth of potential to drug research. But first, you’ll need to build an infrastructure to support large-scale data movement.
The 2017 Nobel prize in chemistry marked a new era for scientific research. Three scientists earned the honor with their introduction of cryo-electron microscopy—an instrument that delivers high-resolution imagery of molecule structures. With a better view of nucleic acids, proteins, and other biomolecules, new doors have opened for scientists to discover and develop new medications.
However, implementing cryo-electron microscopy isn’t without its challenges. Most notably, the instrument captures very large datasets that require unique considerations in terms of where they’re stored and how they’re used. The level of complexity and the distinct challenges cryo-EM presents requires the support of a highly experienced Bio-IT partner, like RCH, who are actively supporting large and emerging organizations’ with their cryo-EM implementation and management. But let’s jump into the basics first.
How Our Customers Are Using Cryo-Electron Microscopy
Cryo-electron microscopy (cryo-EM) is revolutionizing biology and chemistry. Our customers are using it to analyze the structures of proteins and other biomolecules with a greater degree of accuracy and speed compared to other methods.
In the past, scientists have used X-ray diffraction to get high-resolution images of molecules. But in order to receive these images, the molecules first need to be crystallized. This poses two problems: many proteins won’t crystallize at all. And in those that do, the crystallization can often change the structure of the molecule, which means the imagery won’t be accurate.
Cryo-EM provides a better alternative because it doesn’t require crystallization. What’s more, scientists can gain a clearer view of how molecules move and interact with each other—something that’s extremely hard to do using crystallization.
Cryo-EM can also study larger proteins, complexes of molecules, and membrane-bound receptors. Using NMR to achieve the same results is challenging, as nuclear magnetic resonance (NMR) is typically limited to smaller proteins.
Because cryo-EM can give such detailed, accurate images of biomolecules, its use is being explored in the field of drug discovery and development. However, given its $5 million price tag and complex data outputs, it’s essential for labs considering cryo-EM to first have the proper infrastructure in place, including expert support, to avoid it becoming a sunken cost.
The Challenges We’re Seeing With the Implementation of Cryo-EM
Introducing cryo-EM to your laboratory can bring excitement to your team and a wealth of potential to your organization. However, it’s not a decision to make lightly, nor is it one you should make without consultation with strategic vendors actively working in the cryo-EM space, like RCH
The biggest challenge labs face is the sheer amount of data they need to be prepared to manage. The instruments capture very large datasets that require ample storage, access controls, bandwidth, and the ability to organize and use the data.
The instruments themselves bear a high price tag, and adding the appropriate infrastructure increases that cost. The tools also require ongoing maintenance.
There’s also the consideration of upskilling your team to opera te and troubleshoot the cryo-EM equipment. Given the newness of the technology, most in-house teams simply don’t have all of the required skills to manage the multiple variables, nor are they likely to have much (or any) experience working on cryo-EM projects.
Biologists are no strangers to undergoing training, so consider this learning curve just a part of professional development. However, combined with learning how to operate the equipment AND make sense of the data you collect, it’s clear that the learning curve is quite steep. It may take more training and testing than the average implementation project to feel confident in using the equipment.
For these reasons and more, engaging a partner like RCH that can support your firm from the inception of its cryo-EM implementation ensures critical missteps are circumvented which ultimately creates more sustainable and future-proof workflows, discovery and outcomes.With the challenges properly addressed from the start, the promises that cryo-EM holds are worth the extra time and effort it takes to implement it.
How to Create a Foundational Infrastructure for Cryo-EM Technology
As you consider your options for introducing Cryo-EM technology, one of your priorities should be to create an ecosystem in which cryo-EM can thrive in a cloud-first, compute forward approach. Setting the stage for success, and ensuring you are bringing the compute to the data from inception, can help you reap the most rewards and use your investment wisely.
Here are some of the top considerations for your infrastructure:
- Network Bandwidth
One early study of cryo-EM found that each microscope outputs about 500 GB of data per day. Higher bandwidth can help streamline data processing by increasing download speeds so that data can be more quickly reviewed and used. - Proximity to and Capacity of Your Data Center
Cryo-EM databases are becoming more numerous and growing in size and scope. The largest data set in the Electron Microscopy Public Image Archive (EMPIAR) is 12.4TB, while the median data set is about 2TB. Researchers expect these massive data sets to become the norm for cryo-EM, which means you need to ensure your data center is prepared to handle a growing load of data. This applies to both cloud-first organizations and those with hybrid data storage models. - Integration with High-Performance Computing
Integrating high-performance computing (HPC) with your cryo-EM environment ensures you can take advantage of the scope and depth of the data created. Scientists will be churning through massive piles of data and turning them into 3D models, which will take exceptional computing power. - Having the Right Tools in Place
To use cryo-EM effectively, you’ll need to complement your instruments with other tools and software. For example, CryoSPARC is the most common software that’s purpose-built for cryo-EM technology. It has configured and optimized the workflows specifically for research and drug discovery. - Availability and Level of Expertise
Because cryo-EM is still relatively new, organizations must decide how to gain the expertise they need to use it to its full potential. This could take several different forms, including hiring consultants, investing in internal knowledge development, and tapping into online resources.
How RCH Solutions Can Help You Prepare for Cryo-EM
Implementing cryo-EM is an extensive and costly process, but laboratories can mitigate these and other challenges with the right guidance. It starts with knowing your options and taking all costs and possibilities into account.
Cryo-EM is the new frontier in drug discovery, and RCH Solutions is here to help you remain on the cutting edge of it. We provide tactical and strategic support in developing a cryo-EM infrastructure that will help you generate a return on investment.
Contact us today to learn more.
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096719/
https://www.nature.com/articles/d41586-020-00341-9
https://www.gatan.com/techniques/cryo-em
https://www.chemistryworld.com/news/explainer-what-is-cryo-electron-microscopy/3008091.article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067001/