Updates - SBAmin.com / Samir Amin

Accelerating Stem cell generation

noreply@blogger.com (SBAmin) — Mon, 09 Nov 2009 09:21:14 PST

Hanna, et al. at Rudolf Jaenisch’s lab in MIT have discovered an approach to speed up generation of induced pluripotent cells (iPS), importantly with efficiency rate approaching ~ 100%. Low efficient rate of transformation was one of the biggest obstacle so far in iPS creation. In a news story at nature.com, lab reported to develop a sophisticated system to study reprogramming using genetically identical mouse immune cells that contain additional copies of four genes (namely, Oct4, Sox2, Klf4 and c-Myc) required for reprogramming. I’ve yet to read details of this system. In brief, using this four genes and their system, they document nearly all cells being transformed to iPS at variable rate of cell division – some transforming early and other at late time-point. Mechanism of variable rate transformation is unclear but this means that all adult cells can be reprogrammed and reprogramming is a continuous dynamic process rather possible cessation after certain time-period in a given cell with those four reprogramming genes. Further, investigating role of oncogenes in iPS, they showed that inhibition of the p53/p21 pathway or over-expression of Lin28 increased the cell division rate and resulted in an accelerated kinetics of iPS cell formation. Interesting to learn, Nanog over-expression transformed cells into iPS at faster rate without significantly affecting cell division, implying cell-division independent mechanisms of reprogramming – yet to be discovered! Team is investigating role of epigenetic events in cell-division dependent and independent models of adult cell reprogramming.

Related resources:

1. Abbott A, Faster route to stem-like cells, Nature News 10.1038/news.2009.1070 (8-Nov-2009)

2. Hanna J, et al., Direct cell reprogramming is a stochastic process amenable to acceleration, Nature AOP: 10.1038/nature08592 (8-Nov-2009)

Bob and his cancer world!

noreply@blogger.com (SBAmin) — Wed, 07 Oct 2009 14:03:55 PDT

Dr Weinberg presenting annual Albright symposium lecture on Cancer World at Harvard Medical School
Samir

This email is sent via my mobile phone. Please pardon the brevity and any typos.

Reprogramming The Cell: Part 6 | First live mammalian body from iPS

noreply@blogger.com (SBAmin) — Thu, 23 Jul 2009 11:36:47 PDT

Nature magazine has just released news about two independent studies in China documenting first successful creation of live mammalian body (mice) from induced pluripotent cells (iPS) derived from mouse fibroblasts. The mouse was named Xiao Xiao or 'Tiny'. Success rate of one team was 1.1% and 3.5% for another. Recent studies showed gene expression signature difference between embryonic stem cells (ESCs) and iPS which means iPS cells behave and act differently than ESCs even though end result is creation of entire mammalian body. This property is important to be taken into account of possible benefits or adverse events associated with iPS use in therapeutic cloning. Ethical concerns would now be more amplified about possible use of iPS in human cloning.
--
Further reading:

1. Nature News: David Cyranoski, Mice made from induced stem cells, Published online 23 July 2009 | Nature | doi:10.1038/460560a

2. Xiao-yang Zhao, et al., iPS cells produce viable mice through tetraploid complementation, Nature advance online publication 23 July 2009 | doi:10.1038/nature08267

3. Kang Lan, et al., iPS Cells Can Support Full-Term Development of Tetraploid Blastocyst-Complemented Embryos, Cell Stem Cell 23 July 2009 | doi:10.1016/j.stem.2009.07.001
--

Ideas @ MIT

noreply@blogger.com (SBAmin) — Sat, 04 Apr 2009 12:43:32 PDT

Following are two of many projects at MIT which are drawing much attention and promise science has to offer in coming years.

1. Sixth Sense – WUW Wear Ur World by Pranav Mistry, Pattie Maes media lab.

A TED talk showing a wearable device with a projector worth $ 350 that paves the way for profound interaction with our environment. Imagine "Minority Report" and then some. More at TED talk video.

2. Virus-powered lithium battery by Angela M. Belcher’s lab

Three years ago, Belcher’s lab reported genetically engineered viruses that could build an anode by coating themselves with cobalt oxide and gold and self-assembling to form a nanowire. More challenging task was to generate green cathode terminal which needs to be more conductive in contrast to relative non-conductive property of biological candidates for such cathode terminal. Now, same team has come up with a novel biological cathode by genetically engineered viruses that first coat themselves with iron phosphate, then grab hold of carbon nanotubes to create a network of highly conductive material. Connecting these cathode and anode: Voila! Virus-powered lithium ion battery! Besides being green alternative to existing technology, such batteries are light-weight and could be charged and discharged at least 100 times without losing any capacitance. Team is working currently to develop manganese phosphate and nickel phosphate based prototype to match and then possibly to overcome current battery standards. Wow, isn’t it?

Additional reading:

1. MIT Press release: New virus-built battery could power cars, electronic devices, Apr 2, 2009

2. Lee YJ, Belcher AM, et al., Fabricating Genetically Engineered High-Power Lithium Ion Batteries Using Multiple Virus Gene, Science 10.1126/science.1171541 (Apr 2, 2009)

3. Nam KT, Belcher AM, et al., Virus-Enabled Synthesis and Assembly of Nanowires for Lithium Ion Battery Electrodes, Science 312 (2006):885-888, DOI: 10.1126/science.1122716

Image copyrighted by MIT, Cambridge MA USA

Changing Status Quo ? 12 letter DNA

noreply@blogger.com (SBAmin) — Mon, 23 Mar 2009 20:18:56 PDT

Leading Synthetic Biologist, Steven Benner, Ph.D. has proposed 12 letter system instead of traditional 4 letter or nucleotides (A,G,C,T) system to define and synthesize artificial DNA at the 237th National Meeting of the American Chemical Society (ACS). According to Fox news report, Benner's new nucleotides, which he and his colleagues have named Z, P, V, J, Iso-C, Iso-G, X and K, are reshufflings of the constituents of those molecules found in our DNA. I am not able to read his original transcript yet but following press release at EurekAlert! and his profile page is giving brief background on 12 letter system. He has to say something very interesting and challenging task when asked about synthetic life, quote:

"But it still isn't self-sustaining," Benner explains. "You need a graduate or post-doc to come in the morning and feed it. It doesn't look for its own food. No one has gotten that first step to work. If you start making estimates of how many molecules you have to look for in order to find one that does this, you're talking about 10,000,000,000,000,000,000,000,000,000,000,000 molecules."

Well! It means mother nature is giving hint to think in a different way to solve the riddle of life.

The Ideal Diet – quantity and not quality matters?!

noreply@blogger.com (SBAmin) — Wed, 25 Feb 2009 20:49:17 PST

One of the most commonly asked question to physician is about the ideal diet person should take. High carbohydrate, Low fat, High proteins; Moderate Carbohydrate and fat with average protein intake, etc. Research led by Harvard School of Public Health in collaboration with Louisiana State University and NIH showed nothing of all those macronutrients’ proportion matters and what really matters is daily calorie intake. Study published in NEJM today quotes “Reduced-calorie diets result in clinically meaningfulweight loss regardless of which macronutrients they emphasize.” Study enrolled 811 overweight adults and data was analyzed after two year follow-up.

Frank M. Sacks, M.D., Bray GA, MD, Williamson DA, Ph.D, et al. Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates, New Engl J Med (2009) 360:859

Press report and critique can be read at following CNN news article.

Darwin 200: Elusive Evolution

noreply@blogger.com (SBAmin) — Thu, 12 Feb 2009 17:16:19 PST

Pillars of Creation (Eagle nebula M16; image by NASA)

On Charles Darwin’s 200th birthday, evolution theory is being revisited by leading science magazines as well as media. I was going through couple of articles and thought to share some of points me and my colleagues discussed during lunch-time.

1. We agreed with NY Times article on why Darwin’s theory remains to be so influential. Article quotes…

One of Darwin’s advantages was that he did not have to write grant proposals or publish 15 articles a year. He thought deeply about every detail of his theory for more than 20 years before publishing “On the Origin of Species” in 1859, and for 12 years more before its sequel, “The Descent of Man,” which explored how his theory applied to people.

2. Personally, I am yet to be convinced how the theory of natural selection can explain enormous complexity and fine-tuned human biological system. From a single cell amoeba to multi-cellular, multi-functional system to evolve over a billion year or say infinite timeline is hard for me to digest, especially considering existing genomic facts, hypothesis and pseudo facts. Nature magazine has special Darwin 200 series in which one of the article mentions about inheritance of culture or social behavior in evolution. That’s just one of the argument and could be the possibility. Even with behavioral inheritance, there needs to be more than just natural and sexual selection for evolution to mature to existing point. Why? I do not have answer to this because…

I have not been much into evolution research and hence, lacks fundamental knowledge behind the Darwinian theory and post-theory research and validation of theory.
Selection by mutation, dna recombination, genetic drift and environmental adaptation certainly have critical role but as all roads lead to Rome, it’s all within DNA – the mother code. Famous cell biologist Dr Ken Miller has very good and convincing example of mutant Flavobactrium which grow on waste plastic material by producing entirely new enzyme (and so its gene) – Nylonase. Again, it’s a frame-shift mutation and DNA! It’s too good to be true for me to project this validation to explain complex human machine. I will not be surprised if we see something very different, a DNA-independent platform explaining theory of evolution and hope it can explain theory behind the first life (and life of that famous first hen or egg)

With that said, I am not a pro-intelligent design person and fail to agree with idea of something supernatural. There are fundamental reasons behind so called, irreducible complexity and although they are not correctly validated on anvil of current scientific platform, I firmly believe that these reasons will be validated in future rather I start drifting away from real definition of Science and lean towards something supernatural. Being agnostic personally, my firm belief comes from the almighty telling me that there is something within the system itself that remain hidden till the eureka day!

Rise of Machines – Genome Sequencing in minutes

noreply@blogger.com (SBAmin) — Tue, 10 Feb 2009 09:02:39 PST

It’s worth sequencing our personal genome if we see what these companies are promising in coming year: Whole genome sequencing in three minutes or for $ 5000 or less at an single base level error rate of less than 0.0033 % ?!?!?

Read complete story at Nature News: Hayden EC, Genome sequencing: the third generation, 6-Feb-2009, doi:10.1038/news.2009.86

One Year Ago: "Sometimes there are nights like this"

noreply@blogger.com (SBAmin) — Mon, 19 Jan 2009 21:00:01 PST

…I know how hard it is. It comes with little sleep, little pay, and a lot of sacrifices…

…We are choosing hope over fear…

…For many months we've been teased, even derided, for talking about hope. We always knew that hope is not blind optimism. It's not ignoring the enormity of the task ahead or the roadblocks that stand in our path. It's not sitting on the sidelines or shirking from a fight. Hope is that thing inside us that insists, despite all the evidence to the contrary, that something better awaits us if we have the courage to reach for it, to work for it, and to fight for it.

Godspeed Mr. President Obama!

Courtesy: Christopher Hass at BarackObama.com

Boston welcomes icy new year!

noreply@blogger.com (SBAmin) — Wed, 31 Dec 2008 21:16:32 PST

Happy New Year to Everyone!

Image courtesy: WBZ TV (link | Fireworks at Boston Commons)

Cellular Reprogramming and iPS: Breakthrough discovery of 2008

noreply@blogger.com (SBAmin) — Sat, 20 Dec 2008 23:13:43 PST

Science magazine has a special issue (Dec 19) detailing breakthrough inventions of year 2008. Indisputably, honor goes to Reprogramming of Cell. This is becoming one of the hottest and most promising area of biological research in coming years. Considering release of sanctions on the gold standard embryonic stem cell research in upcoming Obama’s administration, it would be interesting to see how much priority researchers will give to induced Pluripotent Cells (iPS).

The Dogma Prevails

noreply@blogger.com (SBAmin) — Thu, 18 Dec 2008 17:51:08 PST

Diversity in biology = permutation of four letters or beyond ??!?

Phenomenon of Polyandry – Justified?

noreply@blogger.com (SBAmin) — Thu, 20 Nov 2008 23:13:16 PST

Besides having fun and frustration in the research, project could emerge from a random thought: Why female of most species, including many mammals mates with multiple male partners? – A term known as ‘Polyandry’. At first, some of us might call as a weird thought until it get published in Science magazine. Price, Wedell, et al. showed possible reasons of such behavior in one of drosophila species. Team showed increased behavior of female flies to mate with multiple male partners because many of male flies were carrying sex ration-distorting gene on chromosome X which lead to failure of male sex expression (on Chromosome Y) and producing sperm infertility and more and more female progeny. Hence, to avoid spreading such selfish gene (from male!) in the offspring and to balance sex ratio, female flies try to mate more often and thus, increasing her chance to mate with normal male to produce healthy offspring. Similar selfish genetic elements may exist in humans. Implications ?!?

Moral of story: Female > Male !

References:

Price TA, Wedell N, et al. Selfish Genetic Elements Promote Polyandry in a Fly, Science 2008:322(5905);1241-1243, DOI: 10.1126/science.1163766
Research sheds light on benefits of multiple mates, EurekAlert! 20-Nov-08

Exoplanets – Quest for the other life continues…..

noreply@blogger.com (SBAmin) — Thu, 13 Nov 2008 22:11:30 PST

Scientists at NASA just published first ever photographs of exoplanets – planets outside of our solar system, captured by the all-time great – Hubble Space Telescope!

Mark S. Marley, Exoplanets—Seeing Is Believing. Science DOI: 10.1126/science.1167569 (EPub-ahead of print) | 13-Nov-2008

Image reproduced from CNN.com article(Image copyright: NASA)

The Next Lipitor

noreply@blogger.com (SBAmin) — Wed, 12 Nov 2008 00:43:32 PST

Following major setback of CETP (Cholesteryl ester transfer protein) inhibitor - torceptrapib by Pfizer in Dec 2006 and an ending era of Lipitor monopoly, the next LDL reducing agent is nearly stepping into phase 1 clinical trail as early as next year. Using RNAi phenomenon, research collaboration between UT Southwestern Medical Center and Alnylam pharmaceuticals team (Philip Sharp and team) ¹ have come up with method to target gene named, proprotein convertase subtilisn/kexin type 9, or PCSK9 – mutation of which is responsible for third form of autosomal dominant familial hypercholesterolemia (HCHOLA3). Using similar RNAi targeted approach, company has shown (Nature magazine article) reduction of apolipoprotein B (apoB) protein and thus lowering of LDL by at least 60 % and total cholesterol reduction upto 85 % in a pre-clinical models. Company is expecting to launch phase 1 clinical trail by early 2009.²

References:

1. Alnylam pharmaceuticals: Programs

2. Pollack A. The Promise and Power of RNA | The New York Times: Nov 10, 2008

Obama on Science & Research

noreply@blogger.com (SBAmin) — Thu, 20 Nov 2008 23:15:26 PST

Following are quotes from the president-elect Barack Obama in his pre-election interview to Nature magazine¹ in September 2008.

“…hundreds of thousands of embryos stored in the United States in in vitro fertilization clinics will not be used for reproductive purposes, and will eventually be destroyed. I believe that it is ethical to use these extra embryos for research that could save lives when they are freely donated for that express purpose.”

“…Recent discoveries indicate that adult skin cells can be reprogrammed to behave like stem cells; these are exciting findings that might in the future lead to an alternate source of highly versatile stem cells. However, embryonic stem cells remain the 'gold standard', and studies of all types of stem cells should continue in parallel for the foreseeable future.”

Let’s all hope the change will come soon and so will be the translation from basic research to clinical cure.

1. Original article:

US election: Questioning the candidates. Nature 455, 446-449 (2008) | doi:10.1038/455446a

HOPE WINS FINALLY

noreply@blogger.com (SBAmin) — Tue, 04 Nov 2008 21:09:31 PST

Many congrats to the one who believed in the faith factor.

Best Regards & more success ahead
Regards,
Samir

PS: This message is sent via mobile device and may contain short text message format.

A little X ray machine inside (Scotch) tape

noreply@blogger.com (SBAmin) — Fri, 24 Oct 2008 12:26:26 PDT

Researchers from UCLA have discovered something very amazing in particle physics. Dr Putterman’s lab have confirmed earlier (and mostly anecdotal) reports postulating emission of X rays while peeling off common adhesive tape (Scotch® branded) from its adhesive surface. Their custom made mechanical motor driven apparatus demonstrated burst of nearly 300, 000 X ray photons lasted for about a billionth of a second, which was sufficient enough to light up closed apparatus system (see video at Nature) and even to take an medical X ray of a finger! In an cover page article of Nature magazine, team explains this phenomenon as triboluminescence - Relative motion between two contacting surfaces can produce visible light (photons) and this concentration of diffuse mechanical energy into electromagnetic radiation, including X rays.

Is there a danger of radiation on keeping office desk tapes?

So far, scientists have showed X ray emission from Scotch tape in a moderate vacuum chamber and not in an open air system. Hence, it is safe for the time being!

Any potential future implications?

Good one: Possibility of research to develop tiny implantable medical device which can burst such electrons to target and destroy tumor cells.

Bad one: Possibility of developing ignition switch to power up nuclear fusion reaction driven by emitting electrons.

References:

1. Camara CG, Escobar JV, Hird JR, Putterman SJ. Correlation between nanosecond X-ray flashes and stick–slip friction in peeling tape. Nature 455, 1089-1092 doi:10.1038/nature07378

2. Chang K. From a Strip of Scotch Tape, X-Rays. The New York Times online (link)

Tweaking Light in Cancer Signaling

noreply@blogger.com (SBAmin) — Sat, 27 Sep 2008 16:21:50 PDT

Any idea how we can play around following keywords:

photon, photo-transduction cycle¹, cancer signaling, PI3K, IR^1,2, EGFR², SGLT1², Diabetes³ ?!?

References / Related Articles / Courtesy:

1. Rajala A, et al.: PMID: 18480052, 17272282

2. Faham S, et al.: PMID 18599740; Suarez-Pinzon WL, et al.: PMID 16123347; Wrighton K: NRC 8 (2008)

3. Dr Pradeep R. Shah, MD

4. Image credits:

Background image copyrighted by Nature magazine: Abbott A, Nature 446 (2007)
Cancer Pathway chart from Applied Biosystems, Inc.
The little eye from personal archive

This article by Amin, SB is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 United States License

Driven By Hope: Direct Cell Reprogramming

noreply@blogger.com (SBAmin) — Fri, 29 Aug 2008 01:22:24 PDT

“….We haven’t learned anything that makes me think this is not a solvable problem”

- Douglas Melton, PhD

An astute, dedicated, daring and person driven by hope – Dr Douglas Melton of Harvard Stem Cell Institute is once again in media by making first successful direct cell reprogramming of adult mice exocrine pancreatic cells into cells resembling islet beta cells and producing insulin as well as improving local vasculature to control hyperglycemic state in-vivo. Unlike islet beta cells reprogrammed from embryonic stem cells or induced pluripotent cells (iPS), direct cell reprogramming technique bypass complete reversal of epigenetic code and instead, research lead by postdoc Qiao ‘Joe’ Zhou used combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) to yield induced beta cells. Further research, hopefully in coming months-years would focus on reproducibility, specificity, potency and important adverse effects of these transcription factors, if any.

Zhou Q, Melton DA, et al. | In vivo reprogramming of adult pancreatic exocrine cells to bold beta-cells | Nature advance online publication 27 August 2008 | doi:10.1038/nature07314

Image courtesy: Zhou Q, Melton Lab | News release at Harvard.edu

About Dr Melton: A person who once volunteered as a glass-washer in a wet lab to satisfy his bench work hunger, Doug Melton has a remarkable and inspirational story of his own which can be read at following links:

1. Driven – Fatherhood focuses Doug Melton's powerful intellect on cure for diabetes | Harvard News | 27-Aug-2008

2. Douglas Melton by Michael J. Fox – TIME 100 (2007)

3. Melton Laboratory

4. Profile: HHMI | Wikipedia