Alzheimer’s illness makes worms stiff and immobile. Professor Jessica Tanis’ group at the University of Delaware discovered something that helped diseased worms retain their wiggle. Tanis and her colleagues have uncovered fresh information on the connection between food and Alzheimer’s disease, the debilitating degenerative brain illness that affects over 6 million Americans. Tanis and her colleagues started looking into the causes and development of Alzheimer’s disease a few years ago. C. elegans is a small soil worm that has been the focus of many investigations in genetics.
After reaching maturity, worms that express amyloid beta, a harmful protein linked to Alzheimer’s, become paralyzed within 36 hours. Even though the worms in Tanis’s lab were made totally immobile, others of the same age in the next petri dish continued to wriggle, which the researchers recorded as “body bends.” Tanis, an assistant professor at UD’s Department of Biological Sciences, said, “It was an observation my master’s student Kirsten Kervin made.” “She kept repeating the experiment and getting the same results,” says the author. Tanis said that after years of work, the team had finally discovered a significant difference. While both strains of E. coli were used to feed the worms, it turned out that one strain contained greater amounts of vitamin B12 than the other. Tanis’s first study looked at hereditary variables, but she later shifted her attention to this vitamin and its potential protective effects.
Worms can teach us a lot about life.
C. elegans is a soil-dwelling nematode, a thin, translucent worm measuring less than a millimeter in length that feeds on bacteria. Due to its much simpler system than humans, this worm has long been used as a model organism for studying cell biology and illness. Numerous research have focused on this worm since the 1970s. This makes it very difficult to figure out how one dietary component influences the development and course of Alzheimer’s disease, according to Tanis. “In this area, though, the worms are really fascinating to see. We utilize genetically identical worms that respond to amyloid beta in the same way people do, and we have complete control over what they consume. This allows us to study the underlying molecular processes at action.” Toxic effects in cells are caused by amyloid beta accumulation in Alzheimer’s patients’ brains over time, resulting in decreased energy, mitochondrial fragmentation, and oxidative stress from an abundance of free radicals. Tanis stated the same phenomenon occurs in C. elegans, although it takes just a few hours. The worms become paralyzed when exposed to amyloid beta.
Tanis described the readout as “black or white”: either the worms are moving or they aren’t. “Vitamin B12 supplementation reduced paralysis in worms with low levels of the vitamin, indicating that B12 was helpful. Additionally, the B12-supplemented worms exhibited greater stamina and less oxidative stress in their tissues.” Methionine synthase, a particular enzyme, is required for vitamin B12 to function. Unless the enzyme is present, Tanis claims that B12 has no impact. Additionally, supplementing the animals’ diets with the vitamin helped only when B12 deficiency was present. Giving animals with normal B12 levels additional B12 has no effect on their health. The researchers also found that supplementing with vitamin B12 had no impact on the worms’ amyloid beta levels.
power of the Tanis group
Tanis praises her pupils’ efforts and accomplishments. A doctoral degree in biological sciences and a master’s in business administration are on the agenda for Andy Lam, the study’s lead author. He worked on the study’s laboratory procedures for many years. He carried out a slew of tests and recorded his findings several times throughout the night. The UD Bio-Imaging Center’s high-throughput technology and deep learning analysis to identify whether or not the worms are moving will be used to automate similar studies in the future. Thus, the team will be able to look into the relationship between food and genetics more quickly as a result of this. To find out what else this chemical route activates, Tanis said, “we basically recognized it.” “ALS and Parkinson’s disease are two examples of illnesses in which B12 may provide protection. We’re taking a look at it right now.”
While Kirsten Kervin earned her master’s degree from UD and now works as a research scientist at WuXi AppTec in Philadelphia, it was her insight into C. elegans that kicked off the endeavor. “My research career at UD has been shaped by a single observation, which Tanis described as “opening up a whole new universe.” It’s a strange experience since I came here expecting to learn one subject and now I’m studying something else. Despite that, it was a difficult process that led to the discovery of a new study topic.” We currently have two PhD students, a postdoctoral research associate, three undergrads, and partnerships with the Bio-Imaging Center and other UD laboratories working on this topic, in addition to others.
A cure for Alzheimer’s disease remains far off, according to Tanis. “You can’t alter your age or your genetic susceptibility to Alzheimer’s disease; there are two things you can’t change. However, you have some degree of influence over one aspect of your life: your diet. It would be great if individuals could alter their diets to slow the development of illness. The researchers in my lab are eager to dig further into this.” Tanis was a pilot investigator for the NIH-sponsored Delaware INBRE program and an Alzheimer’s supplement grant funded by the University of Delaware Research Foundation.
Journal Reference : Andy B. Lam, Kirsten Kervin, Jessica E. Tanis. Vitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycle. Cell Reports, 2021 DOI: 10.1016/j.celrep.2021.109753