Dr. Michael A. Welte
Associate Professor

Department of Biology
University of Rochester
Hutchison 317
michael.welte@rochester.edu

Papers

M.A. Welte, J.M. Tetrault, R.P. Dellavalle, S. Lindquist
"A new method for manipulating transgenes: Engineering heat tolerance in a complex multicellular organism"
Curr. Biol. 3:842-853 (1993)

When organisms are conditioned by exposure to mildly elevated temperatures, they synthesize heat-shock proteins (hsps) and acquire protection against otherwise lethal heat treatments (thermotolerance).  To analyze what role Hsp70, the major heat shock protein in Drosophila, plays in thermotolerance, we developed two new techniques:

Using the yeast FLP recombinase, we created a series of transgenic fly strains that differ only in the copy number of Hsp70.  In particular, we compared a strain carrying only the 10 endogenous Hsp70 genes ("excision strain") to a strain that carried in addition 12 additional copies of Hsp70 ("extra-copy strain").  We then tested if higher levels of Hsp70 affect survival after a severe heat challenge.

Embryos were pretreated at 36°C for various lengths of time to allow them to synthesize heat-shock proteins.  Then they were challenged with a severe heat shock, and their survival was monitored in the hatching assay.


Diagram: Heat-Shock Protein 70 kiloDaltons

At 6 hours of embryogenesis, the extra-copy strain acquires thermotolerance faster than the excision strain.  Once Hsp70 has accumulated to a sufficient quantity to provide as much protection as it can, both strains should survive similarly well.  Indeed, with very long pretreatments (not shown), survival is indistinguishable.

Conclusion:  In early embryos, Hsp70 is rate-limiting for the development of thermotolerance.  And manipulating the expression of a single heat-shock protein can be sufficient to increase the thermotolerance of a multicellular organism.


Perspective

If Hsp70 is so beneficial for stress survival, why does Drosophila not have even more copies of Hsp70 in its genome, i.e., why do we not find extra-copy Hsp70 lines in nature?  Apparently, increased Hsp70 expression also carries a cost, so detrimental and protective effects of Hsp70 need to be balanced. Martin Feder at the University of Chicago has developed a very active research program to unravel the function of Hsp70 in stress tolerance.  Visit Martin Feder's website for exciting new findings about the benefits and costs of Hsp70 expression.

Our transgenic lines have also been used to analyze the effect of thermal conditioning on longevity.  Heat-induced expression of Hsp70 increases lifespan at normal temperatures.