Areas of Focus

Structure, function, and regulation of the mitochondrial calcium uniporter complex (uniplex)

Mitochondria play critical roles in cell metabolism, signaling, apoptosis, and protein homeostasis. Proper regulation of mitochondrial function requires effective communication between the cell and its mitochondria.

Calcium signaling is central to this communication. Calcium primarily enters the Homo sapiens mitochondria through the mitochondrial calcium uniporter complex (uniplex), a highly selective calcium channel located in the inner mitochondrial membrane.

I joined the Sancak Lab in March of 2018 as the lab’s first graduate student. The lab studies the molecular biology and metabolism of mitochondria (shown above) with the hope that this knowledge will improve the diagnosis and treatment of disease. We are also interested in studying mitochondrial (dys)function as a way to identify drug targets and drugging strategies.

My lab, and most of my projects in graduate school, seek to answer two big-picture questions:

1. What does the mitochondrial uniplex do beyond regulating energy (ATP) production within the cell?

2. How is the uniplex itself regulated?

The interplay between calcium, protein binding, and protein stability

My other projects in graduate school are broadly focused on examining the role of calcium in the regulation of mitochondrial and cellular signaling, particularly as this signaling arises from protein-protein interactions.

Mechanistically modeling the influence of temperature on Arabidopsis thaliana flowering

When I first moved to Seattle, I was very fortunate to find a research assistant position in the University of Washington’s Biology department, in the Imaizumi Lab. This experience helped me find my job in biotech and get into graduate school. The impetus for my project centered on improving the widely accepted models of plant flowering time.

Most plant temperature response models are based in the fact that leaf emergence, leaf expansion, and flowering occur more quickly during warm growing seasons than cool ones. This strong correlation between plant development and temperature led to the use of imprecise metrics such as Growing Degree Days (GDD) to predict flowering.

Recent advances in molecular botany provided us with an opportunity to assess the underlying processes involved in plant temperature response. Using a simulation model, we assessed temperature influence on the flowering gene, FLOWERING LOCUS T (FT), which is produced in the leaves before traveling to the shoot apex to induce flowering.

Our simulations suggested that the overall amount of FT, governed by production, influences the developmental stage (leaf number) at which flowering occurs. The rate of whole-plant FT accumulation, governed by leaf growth, influences the day at which this transition occurs. The latter is consistent with the concept of thermal time, while the former helps clarify how variations and interactions in climate factors such as day-length and temperature fluctuations may alter flowering responses.