Dr. Iva Zovkic is an assistant professor of psychology at UTM and an epigeneticist. Along with her team, she has pushed boundaries in the field of epigenetics. For this issue, The Medium sat down with her to discuss her ground-breaking research.
Epigenetics, a relatively new and constantly evolving field, examines how gene expression can transform and contribute to change in an organism. One area in which Zovkic and her team are working towards unwinding is the study and understanding of genetic variances in memory. They are focusing on how a change in gene expression occurs due to a certain event and how that influences memory formation.
Histones are proteins that package DNA into structural units called nucleosomes. “What we don’t know is how histones can be modified in complementary ways to regulate gene expression at the level of the nucleus,” Zovkic says. Histone modification is “highly sensitive to environmental stimuli [including] things that are happening in the rest of the cell [and] signaling mechanisms.”
The category of epigenetic modification Zovkic and her lab is known for is “histone variant exchange in the brain [which] is something no one has looked at before.” Histone variant exchange is when “you can take [the] histones that make up the nucleosome [and] swap them out with different type of histones [resulting in a] change [in] function.” Zovkic mentions that while histone variant exchange “is something that is widely studied in relation to cancer, it has never been studied in the brain before.”
Zovkic’s lab is focusing on the H2A family of histones. The switching on and off of genes, specifically by the H2A.Z histone is a huge factor in memory retention. A paper published by Zovkic in Nature in 2014 was the first to “show that histone variants influence membrane[s].” Zovkic explains that “what we found is that [when] H2A.Z is bound to DNA, it reduces the strength of a membrane. When you learn, H2A.Z actually gets kicked out.” H2A.Z is a break in transcription, and when you remove it, “memory is able to form.”
One of the first times the team observed a change in function due to histones replacing each other was in 2014 when researching fear membranes in mice. Zovkic and her lab found that prior to shocking, mice are excited to explore a box they are placed in. However, when “you give them even a mild foot shock [and] put [the mice] back in the box, the mice normally freeze instead of running around and exploring.”
The most exciting thing Zovkic and her lab have found is that H2A.Z “may have different roles depending on whether [the individual] is a male or female.” While Zovkic and her lab “did show androgen receptors regulate H2A.Z binding to specific genes,” Zovkic emphasizes that these findings have not been published yet, and they still need to determine how and why the effects of H2A.Z are contingent on gender.
Zovkic says that “there is lots left to be explored” including whether H2A.Z “operate[s] the same way in all forms of membrane [and] what the other family members of H2A are doing.” Furthermore, while the genes which encode for memory processing are only active within a short-term window, the consequences last for a long time. Zovkic is trying to determine what occurs in this short-term consolidation window that makes memories persist, even after the genes are turned off. Findings will contribute to “a whole new way to change gene regulation by swapping different histones in a nucleosome.”
Zovkic recently received a $956,000 grant from the Canadian Institutes of Health Research. With the grant, Zovkic and her lab will especially focus on the various roles of the H2A.Z histone contingent on gender, on the histone’s causal effect on Alzheimer’s, and lastly, whether H2A.Z accumulation can impede or improve gene expression.
Science is forever evolving and Zovkic is looking forward to using her discoveries to enhance quality of life. Once her lab is able to characterize the relationships between individuals without Alzheimer’s disease and those with the condition, Zovkic may work with medicinal chemists to apply her discoveries to drug development.
There are several important questions surrounding the effects of H2A.Z on humans. What has been undoubtedly proven thus far is that environmental enrichment is highly beneficial in keeping the mind active. While individuals cannot escape a gene that is activating a condition such as Alzheimer’s, the risk can be minimized through education, engagement, and diversity of environments. However, it is risky to label drugs as wholly negative and always prioritize natural enrichment over drugs and artificial stimuli. In some cases of treating Alzheimer’s, the combined benefits of medicinal drugs and behavioural theory may quite possibly be the key.
