Manisha Premnath

- Doctoral Research-

"Shape shifter" cells:
What makes cells change morphology?
Can we keep them from changing shape?


HIGHLIGHTS:

  • Certain cells show striking and interesting changes in morphology (shape and form)  under different environmental conditions. Such changes in morphology are often associated with important changes in cellular processes, cell function and cell behavior.  For example, it has been observed several pathogenic fungi exhibit their pathogenicity only in certain morphological states. On the other hand, morphogenesis in multicellular organisms is central to the development of tissues and organs. In my PhD thesis, I used a fungus, B. poitrasii, to understand phenomena associated with the process of morphological change.
Change in morphology (shape and form) of cells
- The case of yeast (spherical) to mycelium (filamentous) transition in B. poitrasii -
Yeast
Yeast
transition Transition
Mycelium
Mycelium
  • The morphology of the cells is determined by environmental conditions and their impact on critical cellular processes. For example, in B. poitrasii,  the morphology that cells prefer to exist in depends strongly upon temperature and glucose concentrations.  Corresponding to morphology changes, one also observes significant changes in the processes associated with cell wall metabolism - in particular, we established using protoplast regeneration and biochemical studies that chitin metabolism influences morphological outcome and that levels of chitin synthase (the enzyme that is involved in synthesis of chitin) shows different levels in the different morphological forms.
  • Often the basis of shape shifting lies in differential regulation of cellular pathways and genes expression. For example, in B. poitrasii,  we discovered as many as 8 different chitin synthase genes which were differentially regulated in yeast and mycelium forms and also during the transition from one form to another.
Differential expression of chitin synthase genes in B. poitrasii
 
Differential Expression of CHS genes
  • If we can identify and understand the key cellular pathways and genes whose differential regulation determines morphological outcome in cells, then we should be able to develop methods to externally regulate these cellular processes and genes and thus obtain desired morphologies while discouraging undesirable morphologies (for example, pathogenic morphologies of certain fungi like C. albicans). For example, our discovery that chitin metabolism (in particular, the expression of chitin synthase genes) influences morphological outcome, helped us identify suitable chemical agents (inhibitors) in the presence of which fungal cells exhibited only one morphology preferentially. 


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"Role of cell wall in the dimorphism of Benjaminiella poitrasii"
by Manisha V. Chitnis
(Research Guide: Dr. Mukund Deshpande)
Department of Biotechnology, University of Pune, India
Defense: 7 January 2002; Awarded: 6 January 2003
Abstract of PhD Dissertation (MS Word)