Want to learn about scientific topics without needing a PhD? Check out the Science Simplified blog from TESS Research Foundation! Dr. Tanya Brown, PhD, works with researchers to make science accessible and empower rare disease community members with scientific knowledge. Dr. Brown has over a decade of experience in neurodevelopmental research and is currently the Scientific Director for TESS Research Foundation. Please reach out to her at [email protected] if you have questions or comments.

Thank you to Stephanie E. Ander, Ph.D.,  for writing this story. She is a post-doctoral researcher for the University of Colorado Anschutz Medical Campus.

What is Basic Research and Why is it Useful?

Scientific advances have drastically shaped our modern lives, from the development of medical breakthroughs to the conveniences of our everyday lives. The tangible products of these advances are all around us, from the modern drugs and vaccines that protect us from disease to the ways we entertain ourselves at home with Netflix and microwave popcorn. However, without understanding fundamental laws of nature, these modern technologies could never have been invented.

What is basic research?

Scientific research can be categorized as basic, translational, or clinical.

• Basic research is curiosity-driven and asks fundamental questions (How? What? Why?) about the core building blocks of life. The purpose of basic research is to understand how nature works.
• Translational research is more focused and applies information from basic research to ask how scientists can use this knowledge to improve human health. It takes basic facts of how life works and translates them for use in potential therapeutics.
• Clinical research takes the successes of translational research and tests whether they are safe and effective in treating disease in human clinical trials.

While this pipeline of knowledge from discovery (basic research) to invention (translational research) to application (clinical research) seems straightforward, the flow of knowledge is nonlinear and always under constant refinement as new data from one type of research raises different questions or possibilities in the others.

The value of translational and clinical research is obvious in our everyday lives. Just take a look in your home medicine cabinet, at the over-the-counter drugs we take to treat our allergy symptoms and the antibiotic ointment we apply to a scraped knee. While these are considered simple medicines today, they would not exist without the centuries of basic research to understand how pollen causes seasonal allergies and bacteria cause disease. As such, a steady stream of new basic research discoveries is required to fuel new, innovative applied research.

The COVID-19 mRNA vaccines (made by Moderna and Pfizer-BioNTech) are good examples of how basic research lays the foundations for innovative technologies to improve human health. These FDA-approved vaccines are lipid droplets that deliver a set of instructions (the mRNA) to cells to train the body to fight coronavirus infection and have been shown to be highly protective against severe COVID-19 in human trials. The ingredients for these vaccines are quite simple, but they could never have been made without the fundamental knowledge of molecular biology, virology, immunology, and cell biology that scientists have accrued over centuries of basic science research.

 

This figure highlights some of the important discoveries from basic science research that made the COVID-19 mRNA vaccines possible.

How one basic research study on SLC13A5 opens many windows of opportunity for understanding and improving patient health

In February 2021, Dr. Da-Neng Wang’s research team (at the NYU School of Medicine) published the first report on the 3D structure of the human sodium-dependent citrate transporter (NaCT) protein—the instructions to make this protein are in the SLC13A5 gene. This seemingly obscure research discovery (in part funded by the TESS Research Foundation) carries important implications for patients with SLC13A5 Epilepsy.

The main job of NaCT is to move citrate from the blood into the cell. However, over 40 mutations in the SLC13A5 gene have been identified that hinder NaCT’s ability to work, ultimately causing epilepsy and neurological disease in young children. Now that scientists have the 3D structure of NaCT, they can use it as a map to better pin-point how particular mutations “break” NaCT (please see our previous Science Simplified post for more explanation on genetic mutations and how they cause disease). Armed with this knowledge, we can design specific and targeted therapeutics.

How does using the 3D structure of the NaCT protein inform therapeutic design? Let’s consider an example with two mutations (mutation A and mutation B) that both “break” NaCT, but each mutation breaks a different part of the protein. The healthy NaCT protein “sees” citrate in the blood and “swallows” it into the cell via a special channel in the protein. Mutation A affects the part of NaCT that allows it to capture citrate from the blood—making NaCT unable to “see” the citrate. Mutation B changes NaCT so that citrate cannot enter the cell—essentially making the protein choke on the citrate it cannot “swallow.” While both mutations have the same effect—decreasing the amount of citrate inside the cell— the underlying reasons are different and may require unique solutions to fix the NaCT protein.

 

This figure illustrates the role of the NaCT protein in bringing citrate into the cell and how knowing the 3D structure of the NaCT protein makes it easier to understand how different mutations can “break” the NaCT protein. Both mutations A and B have the same effect of low citrate levels inside the cell, but the reason why this happens is different. Fun fact: the blue protein structure shown in this figure is the actual 3D map built by Dr. Wang’s group of the NaCT protein!

As with any of the great therapeutic breakthroughs, new innovative treatments for SLC13A5 Epilepsy will be fueled by the efforts of basic research. Knowledge is power, and basic research is a never-ending fountain.