Areas of Research
- Apoptosis Research
- Autophagy Research
The Bratton laboratory, located near Austin at Science Park, is primarily interested in two basic areas of research: apoptosis (programmed cell death) and autophagy (self-cannibalism). Apoptosis is critical for normal development in multicellular organisms from flies to humans, and it works in concert with cell division to maintain the normal size and function of adult tissues.
Diseases associated with increased rates of apoptosis include neurodegenerative disorders (Alzheimer's Disease and Parkinson's Disease), AIDS, myelodysplastic syndromes, and ischemic injury (stroke and myocardial infarction), whereas those associated with inhibition of apoptosis include autoimmune diseases and cancer. In fact, defective apoptosis is a hallmark of cancer and a major cause of resistance during cancer therapy.
Autophagy, on the other hand, is primarily a cell survival rather than a cell death process. In cells deprived of growth factors or nutrients, intracellular proteins and even entire organelles are broken down and proteolytically digested within lysosomes in order to provide energy and macromolecules for essential biosynthetic pathways. Autophagy therefore plays an important role during tumorigenesis, as it allows early solid tumors to survive prior to vascularization (angiogenesis), and it promotes chemoresistance by allowing tumor cells to remove damaged proteins and organelles.
Finally, emerging evidence suggests that cross-talk exists between apoptotic and autophagic pathways, in that established regulators of apoptosis, such as the tumor suppressor p53 and antiapoptotic Bcl-2 family members, also regulate autophagy.
Cryo-EM structure of the Apaf-1 apoptosome and proposed models of caspase-9 recruitment and activation.