Gunter blobel

http://www.rockefeller.edu/labheads/blobel/blobel-lab.html
John D. Rockefeller, Jr. Professor; Investigator, HHMI
The unidirectional translocation of thousands of distinct proteins across specific intracellular membranes is mediated by "signal" sequences. On average, a signal sequence consists of a stretch of ~15 amino acid residues that is either a transient or permanent part of the protein to be translocated. The signal sequence functions essentially as a ligand. Each signal sequence is membrane specific and is decoded by a complex machinery that is restricted in its location to one particular cellular membrane.
Two distinct mechanisms of translocation have so far been discovered. In one mechanism translocation proceeds through protein conducting channels. The diameter of the aqueous center of these protein conducting channels is limited (~2 nm) so that passage of a protein can proceed only in its unfolded configuration. A number of polypeptide binding proteins assist in keeping the protein to be translocated in an unfolded configuration. Protein conducting channels have recently been detected electrosphysiologically in the endoplasmic reticulum and the prokaryotic plasma membrane. These channels were found to be gated open by the signal sequence. The channel closes after translocation of the chain is completed. In addition to opening and closing across the membrane, the channel must also be able to open and close in a second dimension, namely to the lipid bilayer. This is necessary to permit integration of proteins into membranes. A protein to be integrated into the membrane uses a signal sequence to open the channel. Translocation proceeds until a "stop transfer" sequence of the translocating polypeptide chain interacts with the channel to open it laterally to the lipid bilayer. As a result, the segment of the chain that is located in the channel would be displaced into the bilayer with the channel simultaneously closing in both dimensions. Similar protein conducting channels are likely to exist in the outer as well as the inner membrane of chloroplasts and mitochondria, in the thylakoid membrane of chloroplasts, and in the peroxisomal membrane. The great challenge ahead is to isolate and to characterize these protein conducting channels.

The mechanism of protein translocation across the nuclear pore complex (NPC) is distinct from that of translocation across the above-described protein conducting channels. NPCs are huge organelles (estimated molecular mass: 125 million daltons) that are suspended in 100-nm wide circular openings in the nuclear envelope. An NPC can open to 25 nm in diameter. For passage across, proteins do not need to be kept in an unfolded configuration. Unlike protein conducting channels, NPCs are unable to integrate proteins into the lipid bilayer. Furthermore, transport across the NPC is bidirectional. Also, transport is not limited to proteins but includes ribonucleoproteins (RNPs). An in vitro system for signal sequence-mediated protein uptake into the nucleus has been used to isolate and to characterize cytosolic factors that are required for import. Similar in vitro RNP export systems are being developed to study export of RNPs. NPCs have been purified in quantity from yeast. An estimated 100 or so proteins make up the NPC. The challenge ahead here is to understand the structure and function of these NPC proteins and of NPC as a whole.

Pietro De Camilli

Pietro De Camilli is an Italian-American biologist and Eugene Higgins Professor of Cell Biology at Yale University School of Medicine. He is also an Investigator at Howard Hughes Medical Institute.

De Camilli completed his M.D. degree from the University of Milan in Italy. He then went to the United States and did his postdoctoral studies at Yale University.

De Camilli is known for contributions that has been to demonstrate the crucial role of protein-lipid interactions and phosphoinositide metabolism in the control of membrane traffic at the synapse.

He has received several awards and honors for his work. He was elected to the European Molecular Biology Organization in 1987. In 2001, he was elected to the National Academy of Sciences and to the American Academy of Arts and Sciences. In 1990 he received the Max-Planck-Forschungspreis together with Reinhard Jahn (Max Planck Institute of Psychiatry).

During synaptic transmission, neurotransmitter-containing vesicles fuse with the plasma membrane, releasing neurotransmitters into the synaptic space by exocytosis. In the subsequent seconds, vesicle membranes are reinternalized and reused for the next generation of synaptic vesicles. Over the last 25 years, Pietro De Camilli has studied the molecular mechanisms involved in this intricate cycle of membrane traffic and has identified and characterized numerous proteins that participate in the process. Trained as an M.D., he has also made significant contributions toward understanding human diseases of the nervous system that involve autoimmunity against synaptic proteins. Because the synaptic vesicle is a powerful model organelle for studying fundamental mechanisms in membrane-cytoskeletal interactions, membrane fusion, and membrane budding, De Camilli's discoveries are relevant to secretory and endocytic mechanisms in many fields beyond neurotransmission.

Prominent researchers- HHMI

Michael D Ehlers.
http://www.ehlerslab.org/
Michael D. Ehlers, M.D., Ph.D. (Young Investigator 2000) of Duke University Medical Center, aims to determine the molecular mechanisms which regulate the localization and function of NMDA receptors. These receptors play important roles in learning and memory, brain development, and neuropsychiatric disease. Dr. Ehlers will identify new regulatory molecules associated with NMDA receptors, determine the effect of phosphorylation (addition of a phosphate molecule) on these receptors, and determine which domains of the NMDA receptor localize it to synapses (the spaces between adjacent neurons). These studies may provide a crucial step in understanding the function of the NMDA receptors, which may facilitate the design of rational strategies for the treatment of neurologic and psychiatric disease, such as schizophrenia.

Locus coeruleus -the core of our daily life?

the structure of striatum

http://www.ploscompbiol.org/article/info:doi%2F10.1371%2Fjournal.pcbi.0020176

Introduction
The basal ganglia of mammals are made up of several nuclei forming large processing circuits in the forebrain and controlled by mesencephalic dopamine (DA) neurons [1]. The dorsal nigrostriatal DA pathway modulates the cortico–striato–thalamic loop [2] involved in extrapyramidal motor and cognitive functions. The ventral mesolimbic DA pathway supports a variety of behavioural functions related to motivation and reward [3]. The functional diversity of the basal ganglia is mirrored by their involvement in pathological conditions as diverse as Parkinson disease, Huntington chorea, schizophrenic syndromes, and drug addiction. The main inputs of the striatum are the excitatory glutamatergic projections from pyramidal neurons of the cortex [4,5]. The GABAergic medium-sized spiny neurons, which comprise more than 95% of the striatal neurons, give rise to two kinds of projections. A direct “stimulatory” pathway projects to the output structures, internal globus pallidus, and substantia nigra pars reticulata, while an indirect, “depressant” pathway projects to the same nuclei via the external globus pallidus and the subthalamic nucleus [6]. The indirect pathway forms an incoherent feedforward loop (that is in the same direction as the direct pathway but with opposite effect), that modulates the effect of the direct pathway. The balance between those two pathways is crucial for the function of basal ganglia. DA released in striatum potentiates the function of the direct pathway, through D1 receptors, and acts as a psychostimulant (enhancing locomotion and elevating mood). In addition, DA inhibits the function of the indirect pathway through D2 receptors. The disappearance of this control contributes to the clinical symptoms of Parkinson disease.

To find out the function of corpus callosom

In Mechanics of the mind, by Collin Blakemore, I know things about the corpus callosom. there must be a way to pinpoint its function in experimental animals.