Nobel Prize Bio Term Paper

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Yoshinori Ohsumi

By: Alex Eby, Ivan Orellana, Efe Basak, Shivam Kapoor, Alex Trombetta

Early Life

Born in Fukuoka, Japan 1945

This time frame was not only tough for Yoshinori and his family, but for Japan as a whole

Illness and disease strongly dictated his childhood

Multiple interests throughout his childhood

Diseases

Insect Collecting

Stargazing

Strong interest in becoming a Scientist

Born feb 9h, 1945 - youngest of 4 kids Yoshio and mother Shina

https://www.nobelprize.org/nobel_prizes/medicine/laureates/2016/ohsumi-bio.html Two Years prior to the ending of WW2

He strugeled as a child battling many ilness and diseases and if not for is parents urging and the lack of medical

Had he had a well know doctor visit him, he might have become a doctor

Without influence to foster these hobbies, that's exactly what they became

His parents strongly influenced his dream of becoming a scientist

In highschool he was a part of the chemisrty club

College and Graduate School

Enrolled in the University of Tokyo in 1967

Chemistry v.s Molecular Biology

Graduate School (University of Tokyo)

Began working under the direction of Kazutomo Imahori

Transition to work under the influence of Akio Maeda

Graduate School ( Kyoto University)

Increased interest in biological membranes

Married Mariko Nakazawa one short year later

Imohiri specialized in physicochemistry to assess interactions between proteins and nucleic acids

At this time Ohsumi was one of the few sceintis in Japan operating a lab

Under Maeda , I began to study the role of ribosome subunits in protein synthesis

For his second year of doctoral studdies he tranferred becasue Maeda became an associate professor

In my research, I became interested in colicin E3, which is able to pass through the membrane of bacterial cells and instantly inhibits protein synthesis

Tokyo after less than a year. In order to support our new family, she successfully applied to the newly formed Mitsubishi Life Science Institute. I also returned to Tokyo to follow Imahori, who had moved to the Faculty of Agriculture at the University of Tokyo, and I barely managed to finish a thesis to graduate with my PhD

Post-Graduate

Rockefeller University - New York

Mechanism of DNA replication initiation in yeast

Returned home to the University of Tokyo in 1977

Continued a study on the research of yeast, but focused on the vacuole

Was able demonstrate the active transport of amino acids and calcium over the vacuolar membrane

Initiated structural and functional studies of V-type ATPase

University of Tokyo's College of Arts and Sciences (Komaba Campus)

Examined the lytic function of the vacuole

We had first planned to use isolated nuclei in this project using density-gradient centrifugation, but it proved difficult to obtain undamaged nuclei. I noticed a white layer at the top of the tube, and when I looked at this layer under the microscope out of mere curiosity I realised that we were also isolating highly purified vacuoles

At the time, the vacuole was thought of as little more than a garbage dump

My work on protein degradation originates from this research on the vacuole - rare opportunity to start an entirely new subject

This is how my career in autophagy research began in that small laboratory at the University of Tokyo. The whole process, from uncovering autophagy to beginning the characterisation of the Atg genes, was achieved within eight years in Komaba.

Post Graduate Continued

National Institute for Basic Biology

Extended his research to mammals and plants

Classified all 18 genes of autophagy (Atg 2, Atg9 and Atg18)

Tokyo Institute of Technology

Focused on how an autophagosome is formed

Shifted focus to physiological meaning of autophagy

Emphasis on the early stages

https://www.youtube.com/watch?v=Ws0mOmfC9EU

This facility provided an environment very supportive of basic biology, and I selected three researchers to join our team: Tamotsu Yoshimori, originally of Kansai Medical School

collaboration with my wife Mariko's laboratory, which helped with cloning at the Teikyo University of Science, as well as the sequencing of the entire yeast genome in 1996

elucidate the genetic context

We have been focussed one subject, how the autophagosome is formed, through the functional analysis of Atg proteins.

we need to systematically consider cells as they exist in an array of environmental contexts

https://www.nobelprize.org/nobel_prizes/medicine/laureates/2016/ohsumi-bio.html

http://time.com/4516341/yoshinori-ohsumi-nobel-prize-winner/

He’s the fourth Japanese scientist to have won a Nobel Prize for medicine

He’s the first scientist to define cell recycling

Major Scientific Achievements

He was the fourth Japanese researcher to win a Nobel Prize for in this category.

The subject of his research had little information available.

He spent more than twenty years studying yeast cells until he made his big discovery.

Ohsumi managed to find the key genes involved in autophagy.

He faced many illnesses as a child and still managed to keep his interests active.

https://www.nobelprize.org/mediaplayer/index.php?id=2702

One of the key organelles involved in digestion and waste removal is the lysosome. Lysosomes are organelles that contain digestive enzymes. They digest excess or worn out organelles, food particles, and engulfed viruses or bacteria.

Proteolytic enzymes digest protein by aiding in the digestion process, breaking it down into amino acids.

Acid Phosphatase: Lysosomal enzyme that hydrolyses organic phosphates at an acid pH.

Major Awards

· 2005 – Fujihara Award, Fujihara Foundation of Science

· 2006 – Japan Academy Prize, Japan Academy

· 2007 – Science Award, Botanical Society of Japan

· 2008 – Asahi Prize, Asahi Shimbun

· 2012 – Kyoto Prize in Basic Sciences

· 2013 – Thomson Reuters Citation Laureate

· 2015 – Gairdner Foundation International Award

· 2015 – International Prize for Biology

· 2015 – Keio Medical Science Prize

· 2015 – Person of Cultural Merit

· 2015 – Rosenstiel Award

· 2016 – Wiley Prize in Biomedical Sciences

· 2016 – Dr. Paul Janssen Award for Biomedical Research

· 2016 – Nobel Prize in Physiology or Medicine

· 2017 – Breakthrough Prize in Life Sciences

Nobel Winning Research and Background

Yoshinori Ohsumi was awarded a Nobel Prize in Physiology or Medicine in 2016 for his discoveries of mechanisms for autophagy.

Autophagy is a process where the eukaryotic cell can modify and recycle its own content by separating a part of the cytoplasm in a vesicle that is ultimately transported to the lysosome.

He wanted to further explore how the cells recycle in order to survive, and how this affects humans and other organisms.

Yoshinori Ohsumi was awarded a Nobel Prize in Physiology or Medicine in 2016 for his discoveries of mechanisms for autophagy. Christian de Duve was the first to use the term autophagy in the 1950’s. Autophagy is a process where the eukaryotic cell can modify and recycle its own content by separating a part of the cytoplasm in a vesicle that is ultimately transported to the lysosome. He wanted to further explore how the cells recycle in order to survive, and how this affects humans and other organisms.

What is Autophagy?

The word autophagy is derived from Greek words “auto” meaning self and “phagy” meaning eating.

https://www.youtube.com/watch?v=_takaZB1-vg

One of the key organelles involved in digestion and waste removal is the lysosome

A new type of vesicle called autophagosome, contains cytoplasmic contents such as; abnormal intracellular proteins, excess or damaged organelles.

Finally, it fuses with the lysosome, where the contents are degraded into smaller constituents.

This process provides the cell with nutrients and building blocks for renewal

Autophagy is a process where the eukaryotic cell can modify and recycle its own content by separating a part of the cytoplasm in a vesicle that is ultimately transported to the lysosome

Autophagosome is a spherical structure with double layer membranes.

Lysosomes are organelles that contain digestive enzymes. They digest excess or worn out organelles, food particles, and engulfed viruses or bacteria.

Yoshinori Ohsumi’s Experiment

To focus better on protein degradation in the vacuole, Ohsumi decided to study on yeast cells since there relatively easy to study and they are more often used as a model of human cells.

Though yeast cells are small and inner structured are not easily distinguished under the microscope.

Therefore, he cultured mutated yeast lacking vacuolar degradation enzymes and simultaneously stimulated autophagy by starving the cells.

https://www.youtube.com/watch?v=LB4Qi8jCoT8

lacked vacuolar degradation enzymes. Within hours, the vacuoles were occupied with small vesicles, which were not degraded (AbdullGaffar, 2017). The vesicles were autophagosomes and Ohsumi's research proved that autophagy exists in yeast cells. He introduced mutations to yeast cells and then autophagy. It is in this step that he discovered first genes crucial for autophagy.

Major Impacts

Oshumi’s findings proved autophagy as a fundamental process in cells, which have direct impacts to humans health

Discoveries led to a better understanding of how cells recycle its contents

Autophagy linked to processes used in: adaptation, starvation, response to infection, etc

Disrupted autophagy is linked to Alzheimer's and type 2 diabetes

Created a new and important study for biologists

Provides energy in starvation, or eliminate invading bacteria in infections

Too little autophagy in Parkinson's or type 2 diabetes

Add quote

Major Impacts Cont.

"An enthusiastic congratulations to today’s Nobel Prize winner, Dr. Ohsumi's groundbreaking work characterizing the first genes involved in autophagy opened up important avenues of research... teaching us valuable lessons about basic cell survival strategies and how these strategies go awry in disease." – John Pham, Editor of Molecular Cell

https://www.youtube.com/watch?v=OA8UhBOQA-Y

Works Cited

Kolata G, Chan S. 2016 Oct 3. Yoshinori Ohsumi of Japan Wins Nobel Prize for Study of 'Self-Eating' Cells. The New York Times. [accessed 2018 Mar 20]. https://www.nytimes.com/2016/10/04/science/yoshinori-ohsumi-nobel-prize-medicine.html

Nobel Prize and Surgical Pathology - Journals - NCBI. National Center for Biotechnology Information. [accessed 2018 Mar 20]. https://www.ncbi.nlm.nih.gov/labs/articles/28181954/

Tooze, S. A., Hannan, L. A., Marks, M. S., Stevens, T. H., & Schroer, T. A. (2017). Fundamental mechanisms deliver the Nobel Prize to Ohsumi. Traffic, 18(2), 93-95.

Yoshinori Ohsumi - Biographical. Nobelprize.org. [accessed 2018 Mar 20]. https://www.nobelprize.org/nobel_prizes/medicine/laureates/2016/ohsumi-bio.html

Works Cited

Johansen T, Lamark T. 2011 Mar. Selective autophagy mediated by autophagic adapter proteins. Autophagy. [accessed 2018 Mar 20]. https://www.ncbi.nlm.nih.gov/pubmed/21189453

Advanced Information. Nobelprize.org. [accessed 2018 Mar 20]. https://www.nobelprize.org/nobel_prizes/medicine/laureates/2016/advanced.html

Samuelson K. 2016 Oct 3. Nobel Prize Winner Yoshinori Ohsumi: 5 Things to Know. Time. [accessed 2018 Mar 20]. http://time.com/4516341/yoshinori-ohsumi-nobel-prize-winner/

http://crosstalk.cell.com/blog/editors-reflect-on-the-2016-nobel-prize-in-physiology-or-medicine

Works Cited

Petrasek J, Szabo G. 2017 Jan 5. Treatment of Alcoholic Liver Disease Including Emerging Therapies, Novel Targets, and Liver Transplantation. Alcoholic and Non-Alcoholic Fatty Liver Disease:291–311. [accessed 2018 Mar 18] https://www.nature.com/articles/nrgastro.2016.185?WT.feed_name=subjects_alcoholic-liver-disease

Mandal A. What is Autophagy? [accessed 2018 Mar 17]. https://www.news-medical.net/health/What-is-Autophagy.aspx

Kane M. 2016 Oct 3. Editors reflect on the 2016 Nobel Prize in Physiology or Medicine. Home. [accessed 2018 Apr 18]. http://crosstalk.cell.com/blog/editors-reflect-on-the-2016-nobel-prize-in-physiology-or-medicine