Circadian rhythm and variation in small extracellular vesicles

Exosomes have been an ongoing interest for several years. Beginning with my PhD in Edinburgh and continuing in my current position I have published several articles on exosomes. The field is also maturing with a growing appreciation for the complexities of exosomes and related vesicles. Exosomes are formed and released by a specific mechanism from cells. Once released exosomes are difficult to distinguish from other sources of similar vesicles. In many experimental settings it would be difficult to confirm an exosomal origin. To reflect this uncertainty the use of the term small extracellular vesicles was suggested following a broad consultation by the International Society for Extracellular vesicles.

We have recently published an article on two related investigations:

  1. the circadian pattern of small extracellular vesicle release in the urine
  2. possible methods for normalizing biomarkers derived from small extracellular vesicles

Circadian patterns, or rhythms, are natural oscillations in biological processes that repeat roughly every 24 hours. They are widely seen in biological systems but little is known about variations in exosome, or small extracellular vesicle, release. A circadian rhythm is just one source of variation that may contribute to the wide variability seen in biomarker studies of small extracellular vesicles. In this article we suggest that normalization by small extracellular vesicle number may help correct for some of the variability encountered.

Technique and review articles on exosomes

I've studied exosomes since the Summer of 2007 when I did my MSc dissertation project and then PhD in the laboratory of James Dear. When it came time to move on I was fortunate in finding my current position where I could explore new areas without moving away entirely from the exosome field where I had so much experience.

An opportunity to revisit the exosomal field came at the beginning of 2016 when we were invited to write three separate book chapters and review articles on exosomes. The third manuscript, a chapter in the book "Drug Safety Evaluation", has just been published online.

Inevitably the manuscripts have some overlap but they each focus on different aspects of exosomes and their study. The highlight was having a figure from our article in the journal of cellular physiology on the front cover of the issue.

The three manuscripts are:

Urine Exosome Isolation and Characterization is focused on the methods we use to collect, process, and characterize exosomes.

Urine Exosomes: An Emerging Trove of Biomarkers is a review of the potential and challenges in bringing exosome based biomarkers into clinical use.

Quantification of Exosomes is a review of the options available for determining the concentration of exosomes.

Regulation of vesicle uptake

A lipid bilayer, called the plasma membrane, surrounds every cell. This protects the cell from the environment and keeps the insides in. Keeping material contained is important for many aspects of biology. Lipid bilayers form organelles and vesicles within the cell to contain specialized components. For example, powerful enzymes recycle old material in the cell. If not contained these enzymes would wreak havoc. To prevent this lysosomes contain the enzymes, protecting the cellular contents. Material from all over the cell can get added to lysosomes.

Vesicles move material from one place to another. Endosomes move material from the plasma membrane. Endosomes either fuze with lysosomes or recycle back to the plasma membrane. The lipid bilayer of an endosome will join with the plasma membrane. The contents of the endosome exit the cell. The endosome can contain even smaller vesicles. Outside the cell we call these vesicles exosomes.

During my PhD I discovered that exosomes can transfer proteins between kidney cells. Wilna Oosthuyzen continued this work by asking what regulates this process. She discovered that vasopressin regulates exosome uptake in collecting duct cells of the kidney.

It is very gratifying when a study builds on work I published earlier, and particularly when executed so well. I was very pleased to be able to contribute.