Mark E. Bowen, Ph.D. (Assistant Professor)

Intrinsically disordered regions within these essential synaptic proteins are drawn as dashes or lines .  Somwhat unsuprisingly, disorder is at the very heart of human cognition.

The Bowen lab investigates the molecular underpinnings of synaptic transmission.  The regulated communication between neurons underlies all that makes us human: learning, memory and emotion.  When communication goes awry the result is mental illness, neurodegenerative disease and death.  By understanding the molecular basis of synaptic function, pharmaceutical strategies for intervening become possible.

When a neuron receives a signal, in the form of neurotransmitters, it must make a binary decision: to propagate the signal of remain at rest.  The probability of response is tuned based on the history of activity at the synapse.  This tuning occurs in the post synaptic density, a signal processing machine containing hundreds proteins including cytoskeletal elements, receptors, ion channels and their associated signaling proteins, held together by scaffold proteins.

My lab focuses on the understanding the multi-protein assemblage of the postsynaptic density.  Many of the proteins are completely or partially disordered, meaning that they lack stable secondary and tertiary structure in their native state.  This is paradoxical because the activity of most proteins is critically dependent on attaining a unique tertiary structure to position key amino acid residues for molecular recognition and catalysis.  It is now recognized that such intrinsically disordered proteins regulate many critical cellular functions.  My lab seeks to extend this knowledge by studying the structure and dynamics of disordered proteins and multiprotein complexes reconstituted from purified components.  To sort out the experimental and biological heterogeneity in these complex mixtures, we use single molecule fluorescence microscopy to follow individual complexes.  We can use fluorescence microscopy as a structural biology tool to follow protein dynamic motions on the millisecond to microsecond timescale.  To correlate structure with function, we use live cell imaging with genetically encoded fluorophores. 

We aim to understand how nature harnesses the ‘configurational adaptibilty’ of protein disorder to achieve the nuanced regulation of neuronal signaling.  Disorder may regulate the availability of binding sites through structural rearrangement, and determine how scaffold binding partners interact with each other in higher order complexes.  Scaffold proteins are hubs in the network of protein interactions.  By learning the relative weights of interactions at the scaffold, we will come closer to predicting the output of neuronal network.

Highly Motivated Students and Postdoctoral Candidates with a Quantitative, Reductionist Outlook are Encouraged to Apply.