A True Blue Award for Lisa Matchett recognizes her exemplary work in Joint Health and Safety

Lisa Matchett is a Teaching Lab Technician in the Ramsay Wright Building who has been recognized with a True Blue Award for Innovation. The True Blue Award highlights the practices of exemplary faculty and staff who make invaluable contributions to the University every day.

Over the past 13 years, Lisa consistently strived to make Ramsay Wright a safer, healthier environment in her position as Worker Co-chair of the Joint Health & Safety Committee. Through the many changes at U of T, she has kept up-to-date with the latest protocols and legislation. She has been pro-active in scheduling committee meetings, ensuring that building inspections are completed and any deficiencies are brought to the attention of Principal Investigators. She maintained this professionalism even under the added duress of constant renovations in the building and the problems that ensue from outside contractors.

As problems arise, she has responded quickly and confidentially with staff, faculty and students. Lisa collaborates with a team who make the Ramsay Wright building a model for other JHS committees across campus.

Dr Heather McFarlane joins Cell & Systems Biology as Professor and Canada Research Chair in Plant Cell Biology

Dr Heather McFarlane has been appointed as an Assistant Professor in the Department of Cell & Systems Biology starting July 1st, 2019.

Professor McFarlane’s research aims to uncover the mechanisms by which plants sense and respond to the status of the cell wall, with the goal of modifying plant cell walls to advance sustainable agriculture, food security, and next-generation biofuels.

Her multidisciplinary approach integrates cell biology, genetics, transcriptomics and computational modeling of protein sequence evolution to produce a systems level understanding of plant cell wall biosynthesis.

Her excellence in research has led to her successfully competing for a Canada Research Chair Tier II in Plant Cell Biology.

Welcome to the Department, Professor McFarlane!

First events in stem cells becoming the specialized cells needed for organ development revealed by the Mitchell Laboratory

The Mitchell laboratory has revealed the very first step in mouse stem cells turning into the organs of the body. Precise experiments by Dhaliwal, Abatti and Mitchell expose the stability of the KLF4 protein as crucial to KLF4’s ability to activate genes. These findings implicate protein stabilization as a major factor in maintaining control of the stem cell state.

While many previous studies focus on the genes that are turned on or off as stem cells become organs, this study uncovered new mechanisms that initiate differentiation, a process required for organ formation. These mechanisms cause breakdown of the transcriptional activating factor KLF4, releasing stem cells from their immature state.

KLF4 protein binds DNA along with many other proteins to form a complex that activates stem cell genes. Dr Dhaliwal’s experiments reveal that KLF4 protein is extraordinarily stable, and this stability is maintained 1) by interacting with other proteins, 2) by binding DNA and 3) through stimulation by signals that prevent stem cell differentiation. When the stimulating signal is disrupted, KLF4 pulls out of the complex, moves away from the DNA and is broken down in the cytoplasm. Interfering with KLF4 protein breakdown prevents stem cells from differentiating to specialized cells, indicating that KLF4 breakdown is a critical step in beginning the process of organ formation. These findings have important implications for regenerative medicine as building new organs requires a detailed understanding of how stem cells become organs.

Professor Mitchell and Dr Dhaliwal with the crucial instrument for these experiments

The insight for this set of experiments came from an unusual observation in the Mitchell laboratory. While studying enhancers – regions of the genome that act like a dimmer switch to increase or decrease the levels of a gene that are expressed – the Mitchell lab found that eliminating a switch for KLF4 decreased gene expression 17-fold, but surprisingly the levels of protein made from that gene were barely affected. In trying to get to the bottom of this unusual observation, the role of KLF4 protein stability was revealed.

Beyond its role in stem cells, KLF4 is also involved in numerous cancers. The researchers suggest the mechanisms uncovered here may shed light on its role in the development of breast cancer, squamous cell carcinoma and gastrointestinal cancer.

The data they present highlight the importance of studying both gene control and mechanisms that affect protein abundance. Furthermore, this is the first time that transcriptional activating factors have been shown function cooperatively through protein stabilizing mechanisms. These mechanisms are particularity timely to keep in mind as more and more work shifts to a focus on studying gene transcripts – even at the single cell level – since these transcriptomic techniques would not reveal mechanisms that rely on protein stability.

You can read more about these results in the paper: KLF4 protein stability regulated by interaction with pluripotency transcription factors overrides transcriptional control and on the Faculty of Arts & Science website