Matthew Miller
University of Utah, UT·Biochemistry
Every time a cell divides, it must give each daughter cell exactly one copy of every chromosome. Errors in this process are the leading cause of miscarriage and are common in cancer, yet why segregation fails in these settings is still unclear.
- Fields
Biochemistry
Biophysics
Genetics
- Topics
chromosome segregation
kinetochore
microtubules
- Grants
- 1 known grant, through Jan 2031
What they work on
- Define how kinetochores sense mechanical tension and how force alters the binding behavior of this large protein assembly to microtubules, building on Stu2 as a key factor in a tension-sensing pathway.
- Identify additional components of the Stu2-dependent tension-sensing pathway and determine how it is coordinated with other error-correction pathways, combining in vitro reconstitution with genetic tests in cells.
- Determine how microtubule tip structure influences the fidelity of kinetochore attachment, and whether tension-dependent changes in tip structure contribute to mechano-sensing.
- Dissect how mitotic kinases coordinate correction of erroneous kinetochore-microtubule attachments, using new tools that activate these enzymes selectively at kinetochores.
More about the research
The key player is the kinetochore, a large conserved protein machine that attaches each chromosome to spindle microtubules, the dynamic fibers that pull chromosomes apart. Kinetochores must hold on to microtubule tips that constantly grow and shrink, detect wrong attachments, and trigger their correction. How they manage all of this is poorly understood, partly because these fast-changing activities are hard to measure and manipulate.
Why it matters
Chromosome segregation errors occur in nearly all tumor cells and are the leading cause of miscarriages and congenital birth defects in humans. By explaining how cells form, maintain and correct chromosome attachments to the spindle, this work could clarify how far such defects contribute to cancer and other human disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Ajit Joglekar
University of Michigan, MI·Biology
Measure the rate at which a single unattached kinetochore generates the Spindle Assembly Checkpoint 'wait-anaphase' signal, using quantitative experimental data.
Soni Lacefield
Dartmouth College, NH·Genetics
Adapt HyperTRIBE, which tags an RNA-binding protein so it marks the RNAs it contacts, to identify the direct mRNA targets of PATL2, PUM1 and PUM2 in mouse oocytes and early embryos, and test how loss of one protein shifts the others' targets.
Fei Li
New York University, NY·Genetics
Define how low-level transcription of centromeres into RNA is regulated in fission yeast and what role it plays in centromere function and chromosome segregation.
The school
University of Utah: 58 labs on PI Pages, $789M a year on research, 366 research doctorates a year.
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