OHSU

Kretzschmar Lab

Kretzschmar Lab
Front row: Bonnie Bolkan, Doris Kretzschmar, Scott Holbrook
Back row: Marlène Cassar, Sudeshna Dutta, Elizabeth Sunderhaus


CURRENT LAB MEMBERS

Dr. Doris Kretzschmar, Principal Investigator

 

Doris- rot

email Dr. Kretzschmar

 

To analyze our "neurodegenerative" flies, we are using diverse imaging techniques ranging from live cell imaging to electron microscopy, in addition to molecular and behavioral assays.

Sections

For example, the picture on the left is a confocal image showing  the localization of the Amyloid Precursor Protein  and its proteolytic fragments (with green and red fluorescence tags at both ends) within an intact Drosophila brain whereas the picture in the middle is from a movie determining the trafficking of this protein in a living neuron in culture. The picture on the right shows an electron microscopic image from a nuclear aggregate (arrow) caused by the expression of a pathogenic Sca1 protein which is responsible for Machado-Joseph Disease.

Dr. Bonnie Bolkan, Postdoctoral Fellow

Bonnie

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Graduate School: Cornell University

Bonnie's Project:

She has two related projects focusing on the normal functions of homologs of Alzheimer’s Disease (AD) related proteins dBACE and dTau.  BACE-1 is the enzyme that cleaves Amyloid Precursor Protein creating the toxic Aß fragment found in AD plaques.  Hyperphosphorylated tangles of Tau are one of the other pathological hallmarks of AD.  Both BACE and Tau are highly conserved in Drosophila making it a good model to investigate their functions in normal neuronal function.



Tau        

Figure: Knockdown of dTau in photoreceptors results in a progressive degeneration of those photoreceptors.  Overexpression of dTau is able to rescue this degeneration (1wk*). 7µm thick paraffin sections. 

 BACE

Figure : Knockdown of dBace in photoreceptor neurons results in progressive degeneration of the glia in the lamina cortex. GMR-GAL4 control flies show an intact lamina neuropil (la n), which mostly consists of neuronal fibers, and lamina cortex (la c), which houses the cell bodies of the neuronal monopolar cells and various glial cells. The basement membrane, which separates the retina (re) from the lamina, is indicated by the white line in the magnification in the right panels. Vacuoles have formed in the lamina cortex (arrowheads) of GMR-GAL4; UAS-dBACERNAi flies (arrowheads). 7µm thick paraffin sections of 28-day-old flies. Scale bar = 10μm.

 

 

Dr. Sudeshna Dutta, Postdoctoral Fellow

Sudeshna

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Graduate School: University of Maryland, College Park


Sudeshna's Project:


The role of Swiss cheese, the Drosophila homologue of Neuropathy target esterase, in glia development

Neuropathy target esterase (NTE), a molecular target of organophosphates (OP) found in pesticides and nerve gases induce delayed neuropathy (OPIDN) in humans. OPIDN is characterized by axonal degeneration mainly of motoneurons. Similarly, loss of the Drosophila homologue of NTE, Swiss Cheese (SWS) causes progressive neurodegeneration in flies but also glial degeneration. Using both Drosophila and mouse model systems,we are trying to understand the importance of the SWS protein in glia, its regulation in axonal-glial interaction and its pathogenic function in inherited spastic paraplegia and in OPIDN in humans.

 

Sudeshna Brainsection

           Figure: Braindegeneration in sws fly


Dr. Scott Holbrook, Postdoctoral Fellow

Scott

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Graduation School: University of  Oregon


Scott's Project:

My research focuses on the role of the endosomal sorting protein, GGA, in the processing of amyloid plaque precursor protein, (APP). Cleavage of APP at specific sites results in the generation of neurotoxic Aβ protein fragments, consequently, regulation of APP-cleaving proteins is paramount for nervous system integrity. Through the use of confocal microscopy, molecular biology, and Drosophila genetics I am figuring out the function of GGA in targeting APP and APP-cleaving proteins to specific subcellular compartments.

 

                    Cha G4 APP1

                   Figure: Cleavage of full length human APP expressed in the adult drosophila brain :
                   GFP labeled N-terminal APP and RFP-labeled C-terminal APP


Droso Phila, Undercover investigator

fly head

do not email me

Droso Phila's Project:

I investigate human behavior. We like to observe scientists and document on their performance under stress. And we keep wondering why these poor creatures have not developed wings....

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Past Members

  • Jill Wentzell
  • Derek Musashe
  • Alex Bettencourt da Cruz
  • Jakob Tschaepe
  • Jennifer Holliday
  • Katia Carmine-Simmen
  • Mahtab  Niyyati
  • Isabell Schwenkert
  • Laura Reese
  • Thomas Proctor
  • Hanil Quirindongo
  • Priya Mani
  • Mandy Cook