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AKWASI MINTA PHD

This remarkable volume is a testament to the evolution of calcium research within living cells and the profound impact it has had on the field of science. It chronicles the journey from the earliest days of studying calcium within the cell, well before the groundbreaking work of a celebrated Nobel laureate in chemistry, to the creation of innovative "modern fluorescence calcium indicators" that have become indispensable tools in contemporary research and drug screening. These modern indicators primarily utilize UV and green fluorescence, providing a non-invasive window into the world of cellular calcium.

1.Asante Calcium Red-2 (ACR-2) is the name of the first true red-emitting fluorescent CYTOSOLIC (Not in Organelles) calcium indicator with ideal physical properties for cells.

It was made in response to a need for a good red-emitting fluorescent calcium indicator since modern fluorescent calcium indicators were invented and introduced in 1982 by the late Roger Tsien, 2008 Nobel Prize Laureate, Akwasi Minta and Grzegorz Grynkiewicz, following a comprehensive review article on red fluorescent calcium indicators by authors.

See below,

Review Article - Molecular Cell Research, Biochimica et Biophysica Acta, vol 1843, 10, pages 2284- 2306,October 2014.

Title: - New red-fluorescent calcium indicators for Optogenetics, photoactivation and multi-color imaging.

Authors; Martin Oheim, Marcel Van't Hoff, Annie Feltz, Alzu Zamaleeva, Jean-Maurice Mallet and Mayeul Collot.

Currently all useful CYTOSOLIC (Not in Organelles) fluorescent calcium indicators are either green-emitting or ratiometric Ultraviolet-emitting and the article reviewed all the red-emitting calcium indicators from1982 to the time of the review (2014), their physical, biophysical properties and some of their applications to date.

Their conclusion and the reason for my making ACR-2 is summed up in the paragraph below.

Despite good arguments in favor of Ca2+ fluorimetry in the red wavelength band the toolbox for measuring Ca2+ in the red spectral band is comparably empty. With the exception of sonie more exotic probes of no practical importance, the user has the choice between no more than four families of small-molecule chemical Ca2+ indicators (based on rhodamines, BODIPYs, squaraines and cyanines) and not all these probes are commercially available. More importantly, many of these probes do not perform similarly well as their green counterparts.

2.Dedication to the memory of Roger Tsien,2008 Nobel Laurate in Chemistry

Roger was awarded the Nobel prize for his discovery and development of the green fluorescent protein, but his fluorescence career started with the invention of a synthetic fluorescent indicator, ‘Quin-2’, for measuring calcium in cells specifically in the CYTOSOL. The beauty of this invention is that he studied Physics and Chemistry as an undergraduate and earned a PhD in Physiology, but he learned organic synthesis during his graduate studies to design, synthesize and work on how to use it in measuring calcium in cells. He learned organic synthesis in the department of Organic Chemistry in Lensfield Road, Cambridge UK. I was a graduate student in organic chemistry at the same time and saw him attending our seminars and coming to the laboratory after hours. I was surprised when I saw his landmark paper on the design and synthesis of Quin 2, because the chemistry was extensive and elegant for a part-time chemist. He chose fluorescence, the most sensitive form of detection of compounds in the cell, for his invention, and so Greg and I had to advance his invention as synthetic organic chemists to create fluorophores, Fura, Fluo, Indo, etc. I am dedicating ACR-2 to his memory but I have taken advantage of it to describe how he started and how we developed this new and current way of studying calcium in cells.

I have emphasized CYTOSOL because he never liked seeing our dyes in organelles. In fact, most of the red dyes made before ACR-2 either go into the mitochondria because they have a positive charge on a nitrogen or go into membranes because of hydrophobicity.

Roger passed away on August 24, 2016, at a young age of 64 and is missed by many including Dr. Lansing Taylor who wrote a foreword to this book.

3.The book has been divided into five Chapters to include my biography (chapter 5); the design, synthesis and applications of ACR-2,(chapter 4); Red-emitting fluorescent calcium indicators, their importance in biology, the case presented by the authors of the review article, and the flaws in all the red fluorescent calcium indicators they presented and red indicators before ACR-2, (Chapter 3); the story of modern fluorescent calcium indicators since 1982 to 2022, (Chapter 2); the measurement of calcium in cells before 1982, (Chapter1). Introduction to the book and all the chapters begins the chapters. I have only one figure for the appendix, and it is very important for the design of ACR.

The title of this book, “Asante Calcium Red-2 (ACR-2) known commercially as ICR (Ionbiosciences Calcium Red)” a scientific memoir, is the name of a red-emitting synthetic fluorescent calcium indicator which was invented by the author to aid in the promotion of calcium research in drug discovery, pharmacology, physiology and general biology and medicine from green-emitting to red-emitting fluorescence.

I was happy when Dr. Taylor agreed to write the Foreword for the book in memory of Roger because when he started his fluorescence journey in 1982, Dr. Lansing, then a professor at Carnegie Mellon University was leading a novel program for developing fluorescence-based biosensors of cellular physiology and light microscope imaging and had just recruited Alan Waggoner and that was the main fluorescence base in the country. Therefore Dr. Taylor and Dr. Waggoner were his first colleagues in the field.

I am happy he remembered Dr. Waggoner and the late Dr. Haugland for their contribution to fluorescence applications in the country
The introduction starts with the definition of the title of the book and the author, and then proceeds to tell the story of ACR-2.
The story includes the development of ACR-2 as an improvement from its predecessor ACR-1 by structure and properties and its commercialization to ICR.
After that, the first four chapters are introduced with short summaries of their chemistries and the final short chapter, which is the biography of the author is added to conclude the introduction.

About The Book

Scientific memoir

One of the most tantalizing challenges that emerged after the advent of these indicators was the quest to develop red-emitting calcium indicators. Initiated in 1985, these endeavors faced repeated setbacks. This book embarks on a unique exploration, tracing the path of calcium research from its early days to the development of the cutting-edge modern fluorescent calcium indicators that continue to be invaluable in research today.

What Happy Clients Say

“An enlightening journey through the world of cellular calcium research. This book not only captures the essence of scientific discovery but also celebrates the relentless pursuit of knowledge. A must-read for anyone intrigued by the mysteries of the cell. – Dr. Sarah Martinez, Cellular Biologist”

“As a researcher in the field, I found this book to be a treasure trove of insights and historical context. It beautifully narrates the evolution of calcium research and the quest to conquer the elusive red-emitting calcium indicators. A valuable addition to the scientific literature. – Dr. Michael Harrison, Biochemist”

“A captivating and thought-provoking exploration of a field on the cutting edge of scientific advancement. This book not only provides an invaluable historical perspective but also offers a glimpse into the future of cellular research. A highly informative and inspiring read. – Prof. Emily Reynolds, Molecular Biologist”