© 2018 Jeff Woodruff

jeffrey.woodruff*at*utsouthwestern.edu

NL 6.110A, 6000 Harry Hines Blvd. 

Dallas, TX

Follow us

RESEARCH

We use live-cell microscopy, nano-rheology, and synthetic biology to understand oocyte ageing, embryogenesis, and cancer onset.

Ooctye ageing and embryogenesis. Every animal begins its life as a dormant oocyte that experiences a dramatic reawakening upon fertilization.  How does the oocyte stay dormant until fertilization? What happens to oocytes as they age, and how does this lead to infertility? How does fertilization activate organelle assembly and division?

We strive to understand the mechanisms of organelle assembly in the early embryo by studying the nematode C. elegans. We also use purified proteins to build minimal embryonic organelles like the centrosome.

Cancer onset and metastasis. The hallmarks of cancer are well established.  But how does a normal cell become cancerous in the first place?  Dysregulation of a membrane-less organelle called the centrosome can trigger tumor formation and metastasis. 

We aim to understand the mechanisms that limit centrosome size, number, and activity in healthy cells. 

SPECIFIC PROJECTS
Assembly and specificity of membrane-less organelles

Embryos build organelles to compartmentalize biochemical reactions. Classic organelles like the nucleus and the mitochondrion achieve this with a lipid membrane. However, many organelles are not bound by a membrane, like P granules, nucleoli, and centrosomes. Such "biomolecular condensates" comprise scaffolding proteins that phase separate to form liquid-like droplets or hydrogels, which attract specific client enzymes.  How do these condensates assemble and how is specific client recruitment achieved?

 

We want to understand these "rules of attraction" using centrosomes as a model organelle. Centrosomes are of special interest to us, as their formation is triggered by fertilization and thus are defining features of early embryogenesis.

C. elegans embryo
Centrosomes
Minimal centrosome
Centrosome dysregulation in cancer

One pathway to tumorigenesis involves loss of centrosome regulation. Centrosomes are microtubule-nucleating organelles that are needed for chromosome segregation, membrane polarity establishment and cell migration. Cancer cells often display centrosome abnormalities, such as excessive number, size, or microtubule nucleation. 

 

We use in vivo models in combination with our minimal in vitro centrosomes to dissect molecular mechanisms that regulate centrosome size and activity.

Microtubules are stiff cytoskeletal filaments that have intrinsic polarity: a fast growing "plus" end and a slow growing "minus" end. In mitotically dividing cells, microtubules are organized with their minus ends anchored within the centrosomes and their plus ends radiating outward.  How is this universal polarity established?

Microtubule polarity establishment
 
Tuning the material properties  of centrosomes

Centrosomes must strike the right balance between flexibility and rigidity.  They need to be porous and malleable to allow microtubules that are nucleated in the interior to extend outward, but strong enough to resist microtubule pulling forces during spindle assembly and DNA segregation. Then, during mitotic exit, centrosomes dramatically weaken and are ripped apart by those same pulling forces.  How is centrosome strength regulated?