Ajith Madhavan
Assistant Professor, School of Biotechnology, Amrita University
Development of a Phototrophic Microbial Fuel Cell with sacrificial electrodes and a novel proton exchange matrix
If micro organisms can solve Sudoku and possibly have feelings, who is to say that they cannot also solve the planet’s energy crisis? Mr. Madhavan employs micro organisms to produce energy using microbial fuel cell (MFC). Micro organisms go through a series of cycles and pathways in order to survive, including the Electron Transport Pathway (ETP) in which bacteria release electrons which can be tapped as energy. In a two-chambered MFC, micro organisms interact with an anode in one chamber and in the presence of an oxidizing agent in the cathodic chamber scavenges electrons from the cathode. The two chambers are connected by an external circuit and connected to a load. In between the two chambers is a proton exchange membrane (PEM) which transports protons from the second chamber to the first and acts as a barrier for electrons. Therefore, a renewable source of energy can be maintained by just providing your bacterial culture with the proper nutrients to thrive and remain happy and satisfied (assuming they have emotions).
Mr. Madhavan has done extensive work on such MFCs and has experimented with various micro organisms and substrates to achieve high energy production. The phototropic MFC Mr. Madhavan designed using Synechococcus elongates using waste water as a substrate was able to generate approximately 10 mȦ and 1 volt of electricity. Other research in this area has even shown that using human urine can be used as a substrate for certain bacteria to produce enough energy to charge a mobile phone.
Although this microbial technology seems to be the “next big thing” (despite their small size) when it comes to renewable energy sources there is still a lot of work to be done before these bacteria batteries hit the market. As of now the MFCs are still much less efficient than solar cells and the search for the perfect bacteria and substrate continues.
Gokul 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.