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"Nanoscale Architecture of the Human Kinetochore" and "Interplay between antibiotic efficacy and drug-induced lysis leading to enhanced biofilm formation at Sub-MICs"

Biophysics Doctoral Candidates - Kelsey Hallinen and Alex Kukreja
Friday, September 15, 2017
4:00-5:00 PM
1300 Chemistry Chemistry Dow Lab Map
“Nanoscale Architecture of the Human Kinetochore”
Alex Kurkreja, Biophysics Doctoral Candidate
ABSTRACT: The human kinetochore is a multi-protein machine that binds ~20 spindle microtubules (MTs) to drive chromosome segregation during cell division. Although the biochemical bases of the functions that the kinetochore performs to segregate chromosomes are well-understood, defining the underlying mechanisms has proven to be challenging. This is because the kinetochore is highly complex in composition (hundreds of copies of eight protein components), and large in size (a ~200 nm diameter disk-shaped surface). To understand the molecular mechanisms underlying kinetochore functions, its spatial architecture must be defined. Specifically, the nanoscale architecture of its protein components relative to the 25 nm diameter of a MT, and sub-micron scale organization of ~20 such MT attachments over its ~200 nm wide surface must be determined to reveal how kinetochore components interact with one another, with regulatory proteins, and with the MT lattice. Here we investigate the nanoscale architecture of the human kinetochore using FRET microscopy. We initiated this analysis with the MT-binding Ndc80 complex, the linchpin of kinetochore-MT attachment, and the two parallel pathways that recruit it to the kinetochore. Our data elucidate the spatial architecture of the Ndc80 complex and how its two biochemical pathways organize the human kinetochore, establishing a foundation for defining a complete picture of its MT-binding machinery.

“Interplay Between Antibiotic Efficacy and Drug-Induced Lysis Leading to Enhanced Biofilm Formation at Sub-MICs”
Kelsey Hallinen, Biophysics Doctoral Candidate
ABSTRACT: We study E. faecalis biofilm formation at varying concentrations of antibiotic, using subminimal inhibitory concentrations (sub-MICs) of antibiotics on all wild-type biofilms and higher concentrations on mixed populations of both sensitive and drug resistant strains. In this work, we investigate the effects of sub-MICs of ampicillin on the formation and extracellular matrix of E. faecalis biofilms. We found that total biofilm mass is increased over a narrow range of ampicillin concentrations before ultimately declining at higher concentrations. From our mixed population studies, we show that the degree of cooperation between resistant and sensitive cells can significantly alter large-scale properties of the biofilm, such as the ratio of sensitive to resistant cells and the statistical and architectural properties of cell-cell contact topologies.
Building: Chemistry Dow Lab
Event Type: Workshop / Seminar
Tags: Biophysics, Chemistry
Source: Happening @ Michigan from LSA Biophysics