Campus

 

Anita L. Manogaran

Assistant Professor
Wehr Life Sciences, 313
(414) 288-4580
E-mail

B.S., 1996, University of Wisconsin-Milwaukee, Milwaukee, WI

Ph.D., 2003, Marquette University, Milwaukee, WI

Post-doctoral Fellow 2003-2008, University of Illinois at Chicago, Chicago, IL

Research Assistant Professor, 2008-2010, University of Illinois at Chicago, Chicago, IL


 

Protein Misfolding and Prion Biology

 

Protein misfolding is associated with many neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, and Prion disease. In each of these diseases, a normal protein adopts an alternative but stable conformation that favors aggregation. Although there are genetic determinants that influence the formation of this alternative form, in the vast majority of patients the disease is caused by the sporadic misfolding of proteins. The focus of my lab is to understand the cellular mechanisms that underlie spontaneous protein misfolding associated with disease.

To begin to understand how these diseases work, our lab focuses on the formation of prions, which are associated with transmissible spongiform encephalopathies, a family of terminal neurological diseases that includes Creutzfeldt-Jakob disease in humans, and “Mad Cow” disease in cattle. In prion disease, a normally folded protein is converted to an alternate conformation that has the ability to further convert the normal protein into the misfolded infectious form (Fig 1). Although much work has focused on looking at infectivity and propagation of prions,

Conversion of a normal protein to the prion form

Figure 1.  Conversion of a normal protein to the prion form.  Normally folded proteins (circles) undergo a rare but stable conformational change into the prion form (squares).  The altered conformation can convert more normally folded version of the protein into the prion form.

much less is known about the initial phases of prion formation since the appearance rates in mammalian systems is approximately 1 in a million. Therefore, the study of a prion in baker’s yeast, [PSI+], has and will continue to be an important model to facilitate our understanding of prion appearance.


To uncover cellular pathways involved in prion formation, our previous work identified several yeast gene deletions that reduced the appearance of the [PSI+] prion. These gene deletions fell into two classes: one class of genes that are involved in the initial misfolding phases of prion appearance, and another class of genes that are important in later steps of prion formation. Interestingly, both classes of genes encode proteins that are involved in actin polymerization and appear to be required to maintain normal vacuolar morphology. Our current work focuses on both genetic approaches and protein biochemistry to investigate how actin networks and the vacuole play an important role in the multistep process of prion appearance.

 

 

Selected Publications

Manogaran, AL., Hong, JY., Hufana, J., Tydemers, J., Lindquist SL., and Liebman, SW.
2011. Prion formation and polyglutamine aggregation are controlled by two classes of
genes. PLoS Genetics. 7, e1001386

Manogaran, AL., Fajardo, VM., Reid, RJD., Rothstein, R., and Liebman, SW. 2010. Most,
but not all, yeast strains in the deletion library contain the [PIN+] prion. Yeast. 27, 159-166.

Manogaran, AL, Kirkland, KT and Liebman, SW. 2006. An engineered nonsense URA3
allele provides a versatile system to detect the presence, absence and appearance of the
[PSI+] prion in Saccharomyces cerevisiae. Yeast. 23, 141-147.

Selected Teaching Publications:

Mynlieff, M., Manogaran, AL., St. Maurice, M., and Eddinger, TJ. 2014. Writing assignments with a metacognitive component enhance learning in a large introductory biology course. CBE Life Sci Edu 13, 311-321.

 

Courses Taught at Marquette University

BIOL1001 – General Biology 1

BIOL1410 – Biology of Human Diseases

BIOL1930 – Foundations in Biological Inquiry

BIOL2001 – Principles of Biological Investigation

BIOL2301 – Neurobiology

BIOL3501 – Cell Biology

BIOL6005 – Scientific Writing

 

Current Students

 

Dr. Manogaran is currently accepting new Ph.D. students into her lab

 



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Biological Sciences Department

Marquette University, Wehr Life Sciences
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