Educational Level:

Roadmap Objectives:

• • Article: Recurrent de novo point mutations in **lamin A** **cause** **Hutchinson-Gilford progeria syndrome**. Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS. Nature. 2003 May 15;423(6937):293-8
  • Content area/major concepts: This paper identifies the causative mutation for Hutchinson-Gilford syndrome.
    
    Pedigree analysis, Genetic mapping, alternative splicing, mutation.
  • Methods or technology used to obtain data: Microsatellites analysis, FISH, sequencing, RT-PCR, Western blotting, immunofluorescence
  • How the CREATE strategy was used:
  • Biggest teaching challenge: Paper is highly technical with lots of genetic jargon and very compact (all of my students will have completed a general genetics course so the terminology will not be completely foreign).
• • Article: Accumulation of mutant lamin A causes progressive changes in nuclear architecture in **Hutchinson-Gilford progeria syndrome**. Goldman RD, Shumaker DK, Erdos MR, Eriksson M, Goldman AE, Gordon LB, Gruenbaum Y, Khuon S, Mendez M, Varga R, Collins FS. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8963-8.
  • Content area/major concepts: This paper characterizes the effects of the mutation in the lamin-A gene on cells.
    
    cell culture, nuclear architecture, recombinant DNA technology, cell cycle, senescence
  • Methods or technology used to obtain data: Immunoflourescence, Western blot, electron microscopy, DNA transfection
  • How the CREATE strategy was used:
  • Biggest teaching challenge: repetition of techniques
• • Article: A lamin A protein isoform overexpressed in **Hutchinson-Gilford progeria syndrome** interferes with mitosis in **progeria** and normal cells.Cao K, Capell BC, Erdos MR, Djabali K, Collins FS. Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4949-54.
  • Content area/major concepts: This paper goes on to characterize the mitotic defect in cells overexpressing the mutant form of lamin-A (the progerin protein).
    
    Mitosis, progerin and ageing
  • Methods or technology used to obtain data: GFP tagging, FACS analysis, FRIP, FRAP
  • How the CREATE strategy was used:
  • Biggest teaching challenge: distinguishing FRIP and FRAP techniques and understanding what each is testing.
• • Article: Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts. Cao K, Blair CD, Faddah DA, Kieckhaefer JE, Olive M, Erdos MR, Nabel EG, Collins FS. J Clin Invest. 2011 Jul;121(7):2833-44.
  • Content area/major concepts: This paper explores the levels of progerin protein in normal aging cells.
    
    Telomeres, ageing
  • Methods or technology used to obtain data: FACS, immunofluorescence. qRT-PCR, reporter constructs, b-gal assays, microarrays
  • How the CREATE strategy was used:
  • Biggest teaching challenge:
• • Article: Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in **Hutchinson-Gilford progeria syndrome** cells. Cao K, Graziotto JJ, Blair CD, Mazzulli JR, Erdos MR, Krainc D, Collins FS. Sci Transl Med. 2011 Jun 29;3(89):89ra58.
  • Content area/major concepts: This paper identifies a potential treatment for progeria
    
    cell growth, antibiotics, ubiquitination and protein degradation, autophagy.
  • Methods or technology used to obtain data: Pulse chase experiments, Co-immunoprecipitation, ubiquitination assay, inhibition of macroautophagy assay
  • How the CREATE strategy was used:
  • Biggest teaching challenge: the number of new techniques.

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