•   Mailing Address
    The Scripps Research Institute - Scripps Florida
    130 Scripps Way, #2C1
    Jupiter, FL 33458

  •    Shipping Address
    The Scripps Research Institute - Scripps Florida
    130 Scripps Way, #2C1
    Jupiter, FL 33458

  •    Physical Address
    The Scripps Research Institute- Scripps Florida
    130 Scripps Way, #2C1
    Jupiter, FL 33458
  •   Phone and Fax Numbers
    Lab      (561) 228-2146
    Admin  (561) 228-3249
    Fax      (561) 228-2415
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Research


Introduction

Our research aims to understand how the brain receives and processes conscious thought or working memory.  Among the five sensory inputs, we are focused on mechanical touch. How does a biological membrane receive and transduce a mechanical force into a chemical signal or neuronal impulse? And how do anesthetics block the integration of the sensory input? Aberrations to sensory input cause clinical disease including chronic pain and mood disorders.

We use pharmacology and biophysical techniques to understand the molecular underpinnings of neurobiology at the plasma membrane. We have found that ion channels bind phospholipids with ligand-like specificity and that the protein-lipid binding sites reveals a novel target for treating pain and neurological disease. 

Transduction of Mechanical Force in a Membrane 

We are studying non-tension mechanisms of mechanosensation. We have shown lipid rafts act as compartments to inactivate proteins by sequestering them away from activating lipid. When force disrupts the lipid, the proteins find their activating lipid and signal. We call this the lipid mixing theory of mechanosensation. 

 

raft imaging

Top) A kinetic model where force disrupts lipid order compared to a tension model similar to energy stored in a spring. Bottom) Super resolution imaging of GM1 lipid rafts in live C2C12 cells assembling and dissasembling. (Petersen et al. Nature Comm 2016)

PLD cartoon

Left) The enzyme PLD is sequestered away from its substrate phosphatidylcholine (PC) and activator PIP2. After application of mechanical force the rafts are disrupted and PLD mixes with PC. Right) Super resolution imaging shows the average distance between rafts and the PLD activator is only 41 nm. The estimated latency for mixing is ~650 micro seconds (Petersen et al. Nature Comm. 2016). 

Lipid gating of ion channels

We are developing the tools to measure lipids binding to ion channels and the cellular siganaling from lipid agonism. Ion channels harbor lipid binding sites for low abundant signaling lipids. The lipids diffuse in the membrane similar to neurtransmitter signals that diffuse in the synapse. When they bind the channel they cause a conformational change that opens the channel. We are studing the pharmacology and structural underpinnings of lipid gating of ion channels.

Kir Lipid site

Migraine Study

We are conducting a clinical study on Migraines that will be released soon on the Iphone. Detail of the study and how to join will be available shortly.

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