Aug
12
Mon
2013
Dr. Lee Hartwell Session @ Amriteshwari Hall
Aug 12 @ 8:15 pm – 9:15 pm
LeeHartwellLeland H. Hartwell Ph.D.
2001 Nobel Laureate, Physiology & Medicine

Dr. Lee Hartwell received the 2001 Nobel Prize in Physiology / Medicine for his discovery of protein molecules that control the division of cells. He was the President and Director of the Fred Hutchinson Cancer Research Center in Seattle, Washington before moving to Arizona State University’s Center for Sustainable Health.

Dr. Hartwell is also adjunct faculty at Amrita University. He spoke to the delegates at Bioquest from his office in the US, over Amrita’s e-learning platform A-View. Given below are excerpts from his address.

I would like to address the young people in the audience. I know that many of you may have come to this meeting wondering, “How can I become a successful scientist? How can I prepare myself to make a contribution in this world?”

These questions are interesting to me also.

Believe it or not, I am still trying to be a successful scientist. That may surprise you since you probably think that a Nobel laureate must have found the answers. But the problem is that the answers to these questions change with time and the answers are different today than what they were when I began my career fifty years ago. The strategy of the 1960’s doesn’t work so well anymore. What is different now?

First, what we know now is much more. For example, by 1970, no genes from any organisms were sequenced. In 2013, we have the complete sequence of the human genome. Second, not only do we know much more today, accessing that knowledge is easy. Third, obtaining new information is much faster today.

Our rich understanding of science and technology is now needed to solve many serious problems. The human population has reached the size where we are utilizing all available resource of the planet. We are utilizing all of the agricultural land, all of the water, all of the forest and fishing resources. We are also polluting the planet that we live on.

We are polluting the land with fertilizers and pesticides; the oceans with acids and the atmosphere with carbon dioxide. We are using up top soil and ground water, thereby reducing our capacity to feed ourselves. We are using up petroleum, the energy source that our entire economy is dependent on. These are problems we were largely unaware of, fifty years ago. But these are problems that must be solved in your life times.

The big question facing your generation is, how can human beings live sustainably on planet earth. Your two broad goals on sustainability are 1) leave the planet as you first found it for your future generations; don’t use up the resources and don’t pollute the planet 2) everyone deserves to have an equal share of the earth’s resources.

Income strongly determines one’s opportunities in life. Many poor people succumb to chronic diseases and unhealthy environments. This inequality undermines our ability to live sustainably. We can’t ask the poor to leave the planet as they found it if they can’t support their families. Education, healthcare, employment are essential to having a sustainable society.

How can we be a successful scientist in 2013?
1. First choose a problem to solve
2. Ask questions to understand why it is not solved
3. Collaborate with those who can help
4. Develop a solution that works in the real world

Chronic diseases are our major burden and this burden will get worse. Heart disease, diabetes, cancer, dementia and other diseases. The good news is that the chronic diseases are largely preventable and more easily curable if detected early. One question that attracts me is how can we detect disease earlier when it can be more easily cured?

Can we use our increasing knowledge in molecular biology to identify biomarkers for early disease detection?

We need to collaborate very closely with clinicians who care for patients to find out exactly where they need help.

I think if we apply our technology to important clinical questions we will actually save medical expenditure and be well on our way to making a great contribution to society.

 

Aug
13
Tue
2013
Plenary Talk: Biosensor and Single Cell Manipulation using Nanopipettes @ Amriteshwari Hall
Aug 13 @ 10:06 am – 10:49 am

NaderNader Pourmand, Ph.D.
Director, UCSC Genome Technology Center,University of California, Santa Cruz


Biosensor and Single Cell Manipulation using Nanopipettes

Approaching sub-cellular biological problems from an engineering perspective begs for the incorporation of electronic readouts. With their high sensitivity and low invasiveness, nanotechnology-based tools hold great promise for biochemical sensing and single-cell manipulation. During my talk I will discuss the incorporation of electrical measurements into nanopipette technology and present results showing the rapid and reversible response of these subcellular sensors  to different analytes such as antigens, ions and carbohydrates. In addition, I will present the development of a single-cell manipulation platform that uses a nanopipette in a scanning ion-conductive microscopy technique. We use this newly developed technology to position the nanopipette with nanoscale precision, and to inject and/or aspirate a minute amount of material to and from individual cells or organelle without comprising cell viability. Furthermore, if time permits, I will show our strategy for a new, single-cell DNA/ RNA sequencing technology that will potentially use nanopipette technology to analyze the minute amount of aspirated cellular material.

Invited Talk: Probing Estrogen Receptor – Tumor Suppressor p53 Interaction in Cancer: From Basic Research to Clinical Trial @ Acharya Hall
Aug 13 @ 3:26 pm – 3:57 pm

gokuldasGokul Das, Ph.D.
Co-Director, Breast Disease Site Research Group, Roswell Park Cancer Institute, Buffalo, NY


Probing Estrogen Receptor−Tumor Suppressor p53 Interaction in Cancer: From Basic Research to Clinical Trial

Tumor suppressor p53 and estrogen receptor have opposite roles in the onset and progression of breast cancer. p53 responds to a variety of cellular of stresses by restricting the proliferation and survival of abnormal cells. Estrogen receptor plays an important role in normal mammary gland development and the preservation of adult mammary gland function; however, when deregulated it becomes abnormally pro-proliferative and greatly contributes to breast tumorigenesis. The biological actions of estrogens are mediated by two genetically distinct estrogen receptors (ERs): ER alpha and ER beta. In addition to its expression in several ER alpha-positive breast cancers and normal mammary cells, ER beta is usually present in ER alpha-negative cancers including triple-negative breast cancer. In spite of genetically being wild type, why p53 is functionally debilitated in breast cancer has remained unclear. Our recent finding that ER alpha binds directly to p53 and inhibits its function has provided a novel mechanism for inactivating genetically wild type p53 in human cancer. Using a combination of proliferation and apoptosis assays, RNAi technology, quantitative chromatin immunoprecipitation (qChIP), and quantitative real-time PCR (qRT-PCR), in situ proximity ligation assay (PLA), and protein expression analysis in patient tissue micro array (TMA), we have demonstrated binding of ER alpha to p53 and have delineated the domains on both the proteins necessary for the interaction. Importantly, ionizing radiation inhibits the ER-p53 interaction in vivo both in human cancer cells and human breast tumor xenografts in mice. In addition, antiestrogenstamoxifen and faslodex/fulvestrant (ICI 182780) disrupt the ER-p53 interaction and counteract the repressive effect of ER alpha on p53, whereas 17β-estradiol (E2) enhances the interaction. Intriguingly, E2 has diametrically opposite effects on corepressor recruitment to a p53-target gene promoter versus a prototypic ERE-containing promoter. Thus, we have uncovered a novel mechanism by which estrogen could be providing a strong proliferative advantage to cells by dual mechanisms: enhancing expression of ERE-containing pro-proliferative genes while at the same time inhibiting transcription of p53-dependent anti-proliferative genes. Consistently, ER alpha enhances cell cycle progression and inhibits apoptosis of breast cancer cells. Correlating with these observations, our retrospective clinical study shows that presence of wild type p53 in ER-positive breast tumors is associated with better response to tamoxifen therapy. These data suggest ER alpha-p53 interaction could be one of the mechanisms underlying resistance to tamoxifen therapy, a major clinical challenge encountered in breast cancer patients. We have launched a prospective clinical trial to analyze ER-p53 interaction in breast cancer patient tumors at Roswell Park Cancer Institute. Our more recent finding that ER beta has opposite functions depending on the mutational status of p53 in breast cancer cells is significant in understanding the hard-to-treat triple-negative breast cancer and in developing novel therapeutic strategies against it. Our integrated approach to analyze ER-p53 interaction at the basic, translational, and clinical research levels has major implications in the diagnosis, prognosis, and treatment of breast cancer.

 

Aug
14
Wed
2013
Invited Talk: A draft map of the human proteome @ Amriteshwari Hall
Aug 14 @ 10:42 am – 11:30 am

akhileshAkhilesh Pandey, Ph.D.
Professor, Johns Hopkins University School of Medicine, Baltimore, USA


A draft map of the human proteome

We have generated a draft map of the human proteome through a systematic and comprehensive analysis of normal human adult tissues, fetal tissues and hematopoietic cells as an India-US initiative. This unique dataset was generated from 30 histologically normal adult tissues, fetal tissues and purified primary hematopoietic cells that were analyzed at high resolution in the MS mode and by HCD fragmentation in the MS/MS mode on LTQ-Orbitrap Velos/Elite mass spectrometers. This dataset was searched against a 6-frame translation of the human genome and RNA-Seq transcripts in addition to standard protein databases. In addition to confirming a large majority (>16,000) of the annotated protein-coding genes in humans, we obtained novel information at multiple levels: novel protein-coding genes, unannotated exons, novel splice sites, proof of translation of pseudogenes (i.e. genes incorrectly annotated as pseudogenes), fused genes, SNPs encoded in proteins and novel N-termini to name a few. Many proteins identified in this study were identified by proteomic methods for the first time (e.g. hypothetical proteins or proteins annotated based solely on their chromosomal location). We have generated a catalog of proteins that show a more tissue-restricted pattern of expression, which should serve as the basis for pursuing biomarkers for diseases pertaining to specific organs. This study also provides one of the largest sets of proteotypic peptides for use in developing MRM assays for human proteins. Identification of several novel protein-coding regions in the human genome underscores the importance of systematic characterization of the human proteome and accurate annotation of protein-coding genes. This comprehensive dataset will complement other global HUPO initiatives using antibody-based as well as MRM mass spectrometry-based strategies. Finally, we believe that this dataset will become a reference set for use as a spectral library as well as for interesting interrogations pertaining to biomedical as well as bioinformatics questions.

Akhilesh (2)