11/05/2021
By Susan Pryputniewicz

The Biomedical Engineering and Biotechnology program invites you to attend a doctoral dissertation defense by John Lamb on “Tau proteins N-terminal alternative splicing influences aggregation, seeding and toxicity.”

Candidate: John Lamb
Defense Date: Friday, Nov. 19, 2021
Time: 1 to 3 p.m.
Location: This will be a virtual defense via Zoom. Those interested in attending should contact the student (John_Lamb@student.uml.edu) and committee advisor (Garth_Hall@uml.edu) at least 24 hours prior to the defense to request access to the meeting.

Committee Chair (Advisor): Garth Hall, Ph.D., Associate Professor, Department of Biological Sciences, University of Massachusetts Lowell

Committee Members:

  • Mathew Nugent, Ph.D., Associate Dean for Research, Innovation and Partnerships, Department of Biological Sciences, University of Massachusetts Lowell
  • Peter Gaines, Ph.D., Professor, Department of Biological Sciences, University of Massachusetts Lowell
  • Sangmook Lee, Ph.D., Senior Researchers, Department of Biology, Boston College

Abstract:

Neurodegenerative disease represents one of the last big mysteries of modern medicine and despite decades of research, hundreds of clinical trials and billions of dollars, the underlying pathogenesis is still relatively unknown. Several recent studies have now suggested that the microtubule associated protein Tau has structural confirmation could be the key factor in understanding tau associated diseases and that smaller soluble tau oligomers may play a more important role than larger and better known plaques and tangles.

Here we have used a cellular propagation system similar to a prion model to examine the full-length protein, focusing on the function of the alternatively spliced exon 2 (E2) in the tau amino N-terminal projection domain. Mutant cells expressing tau without the E2 domain (E2-) showed accelerated tau aggregation and toxicity along with the highest seeding ability with wildtype tau. In contrast, cells expressing tau containing the E2 domain (E2+) showed reduced seeding activity with less toxicity. In this study we performed additional correlations which suggest that the toxic tau species are relatively large oligomers which also regulate seeding activity. By understanding more about the molecular mechanisms of tau proteins different isoforms we have uncovered new insights into how tauopathies propagate and the sequence of events which are involved in neurogenerative disease.

All interested students and faculty members are invited to attend the online defense via remote access.