High-Throughput Resources for Researchers

Author: David Flaherty

 

Graphical Abstract

High-Throughput Resources for Researchers
High-Throughput Resources for Researchers

Legend. To help make high-throughput technology available to researchers at large, many research institutions have established high-throughput centers that offer these services.Researchers can work alongside these centers to learn how to best incorporate high-throughput techniques into their workflow and gain the benefits of this promising field. Images adapted from GSL and SRMSC websites under fair use for educational purposes. Image created using Canva Pro.

 

Summary of High-Throughput Resources

What is High-Throughput Technology and How Can We Use It?

High-throughput (HT) technology is a rapidly developing field of research. In short, HT technology relies on the use of machine automation and well honed experimental assays to rapidly perform thousands of experiments in parallel (1). While there are many benefits to this type of approach, the main drawback is the initial investment in both equipment and personnel needed to utilize these techniques. To this end, a number of centers have been set up that allow researchers to leverage the benefits of HT technology without the massive upfront cost.

These centers contain all the equipment necessary for normal HT work (liquid handlers, automated workstations, microplate handlers, etc.) and trained personnel to operate and maintain them. They also typically maintain a large chemical database for mass screenings. Their primary focus is to provide these resources to researchers who would otherwise be unable to access them. This is done in exchange for payment for equipment and time, but also research using these centers must acknowledge the center’s support.

To get started, researchers wishing to work with an HT center must first determine what experiment they wish to run and adapt this into an HT assay. Often the center will assist in this process and in selecting controls to help researchers get the best results from the assays (3). At this point, the HT center can run through a portion of their chemical database to see if there are any hits. These hits are validated and putative pathways for the compound’s activity are presented to the researcher. In this way, researchers can rapidly test thousands of compounds utilizing an HT workflow. Included below are a few examples of some major HT resource centers in the US. Though these three are all in the US, there are many more centers worldwide.

 

A Few Examples

Scripps Research High-Throughput Molecular Screening Center (SRMSC)-As our first example, the SRMSC at the Scripps Florida division has the goal of “collaboration with other scientists at Scripps and around the world, identifies drug-like compounds that can help better understand and ultimately cure diseases (2).” To this end, they leverage a chemical database to find leads in drug development. Their services are offered throughout the HT process. They will assist in developing and optimizing HT assays, performing the HT screening, and assisting in data analysis and structure/mechanism identification. For researchers interested in working with the SRMSC they recommend to work through NIH-sponsored mechanisms such as PAR-20-178, an emergency NIH award for rapid investigation into COVID-19 (2).

 

Rockefeller University’s High Throughput and Spectroscopy Center (HTSRC)-The HTSRC “guides researchers in drug discovery (3).” They aim to do this by providing a massive chemical database, assisting with bioassays, and identifying chemicals of interest using applied biochemical techniques. While this sounds similar to the SRMSC, the HTSRC has a stronger focus on basic research and so offers a more robust selection and focus on molecular structure and function. As a result, their services may appeal to a wider range of researchers. However, they are primarily focused on providing their services to researchers within their university system. While this may make them more available to these researchers, it means that outside researchers will have a much more difficult time booking experiments through them. So while the HTSRC may not be the most useful resource for outside researchers, it is a good example to show that not all of these centers are equally open to working with all researchers. A good warning to keep in mind when communicating with these centers.

 

NCSU’s Genomic Sciences Laboratory (GSL)-Finally, we come to a more local and specialized HT center. The GSL here at NCSU is unlike the other two mentioned centers in that it focuses on high-throughput sequencing rather than on drug discovery or basic science (4). While this may not have as wide a range of applications due to its specialization, it is still an important service for many research projects that require high fidelity sequencing en masse. They provide documentation for proper sample preparation and a catalog of free software for post-sequencing analysis. Though they are strongly connected with the UNC system, they do offer their sequencing services to outside entities as well (though no discounts for being a UNC researcher).

 

In Closing

HT technology holds great promise for research, but requires massive upfront investment. To help mitigate this expense, multiple research institutions have developed their own HT centers and offer their services to researchers. These centers can specialize in different aspects of HT technology and who their main collaborators are, but all focus on assisting researchers prepare their experiments for massively parallelized assays, carrying out these assays, and analyzing the data generated. Without these collaborations, HT techniques would likely not be able to be incorporated into a normal research workflow and many researchers would be cut off from the benefits provided by it.

 

References

  • Mishra, P., Ganju, L., Sairam, M., Banerjee, P.K., Sawhney, R.C. A review of high throughput technology for the screening of natural products. Biomedicine & Pharmacotherapy. 62 (2), 94-98 (2008).
  • High Throughput Molecular Screening Center. HTS Scripps. https://hts.florida.scripps.edu/
  • Genomic Sciences Laboratory. NCSU https://research.ncsu.edu/gsl/

 

Audio Recordings

Introduction (0:43)

Resources 1 (2:20)

Resources 2 (3:42)

Questions (1:47)

 

Questions

  • What is a high-throughput resource center? These are centers that provide researchers with access to the equipment and professionals needed to perform high-throughput techniques.
  • Why do researchers need access to these centers? While high-throughput techniques can be very useful, they are also very expensive and require specialized training to be used.
  • List three high-throughput resource centers and what they specialize in. Rockefeller University’s High Throughput and Spectroscopy Center and their focus on drug discovery and biochemical analysis, Scripps Research’s High-Throughput Molecular Screening Center and their focus on drug discovery, and NCSU’s Genomic Sciences Laboratory focus on high-throughput
  • Reflect on the benefits these centers provide and whether or not high-throughput technology would be as widespread without them. These centers provide access to instruments and experiments that would otherwise be unavailable to the vast majority of researchers. This makes them key to the advancement of high-throughput technologies and their increasing incorporation in research
  • How could these centers help to benefit ethics in research? By requiring standardized experimental assays and collaboration, these centers help to foster repeatability. This helps to make research more robust by allowing other researchers to replicate experiments and results more readily and keep open lines of communication.