How cell fates are established and how identities of different cell types are maintained during development of multi-cellular eukaryotes are questions of extreme biological significance at the heart of development. A single-celled zygote undergoes many rounds of mitotic divisions which ultimately lead to generation of over 200 different specialized cell types in human body during development. Although, each cell type contains same basic genetic information (DNA), yet their identity is different from one another which are maintained throughout development. It is known that differential gene expression programs lead to different cell lineages and each cell type remembers its identity due to maintenance of cell type specific gene expression program referred to as transcriptional cellular memory. Transcriptional memory involves changes in the chromatin state of lineage specific genes; changes that can persist through DNA replication and mitosis, which means they are inherited from mother to daughter cells. Such heritable changes are called epigenetic modifications and can be covalent marks on DNA and/or histones, and therefore would not alter the basic genetic information in a cell. However, epigenetic changes may either activate or silence the expression of lineage specific genes and set the stage for differential gene expression among different cell type. This explains how cells with same DNA can acquire different identity which is maintained through epigenetic inheritance during development. In Drosophila melanogaster (fruit flies), genetic analyses have uncovered two groups of genes, the Polycomb Group (PcG) and the trithorax Group (trxG), responsible for maintaining gene expression patterns stably and heritably. Importantly, PcG and trxG proteins are evolutionary conserved and most of our knowledge about their function was pioneered from studies in Drosophila. Molecular analysis showed that many of the proteins encoded by the PcG and trxG act in large complexes, and modify the local properties of chromatin to maintain transcriptional repression (PcG) or activation (TrxG) of their target genes. My lecture will primarily focus on introducing epigenetics, transcriptional cellular memory and how they affect our development.

Cells reside and operate in a complex and dynamic extra-cellular matrix. The mechanical, structural and chemical properties of the matrix regulate a variety of cellular functions including signaling, adhesion, migration as well as invasion and metastasis in tumor systems. Unfortunately cell-matrix interactions have traditionally been studied in the context of artificial 2D environments, which are far from in vivo conditions. As a result, our understanding of the complex interactions at the cell-matrix interface has been quite limited. In particular, the mechano-chemical effects of the matrix, the proteolytic pathways and surface receptor dynamics on a 3D surface that are critical in invasion and tumor metastasis, and can not be fully studied in a 2D environment. In order to overcome the limited powers of observation in 2D, we utilize a combination of high resolution and high throughput confocal microscopy, bulk and micro-rheological measurements and multi-scale simulations rooted in statistical and continuum mechanics. Using an interdisciplinary approach allows us to understand and quantify the mechanical and chemical roles of the matrix in regulating signaling, adhesion and motility. Our results demonstrate that both cell structure and cell function are strikingly different in 3D than in 2D and that cellular response to minor mechanical changes in its extra-cellular environment is amplified in 3D than in 2D environments. Our experimental results are complemented by multi-scale simulations, that probe the physical foundations of cell-matrix interactions from the nano to the macro level. Our hybrid approach, combining high-resolution experimental and computational techniques demonstrates how a balance of cellular parameters (e.g. integrin expression and MMP activity) co-operate with matrix properties (e.g. composition, stiffness and porosity) to regulate adhesion, invasion and motility of tumor cells in native like environments.

The controlled arrangement of DNA molecules on surfaces represents one challenging contribution of nanotechnology to biology and medicine. In particular, one of the open issues in the field of DNA-based sensors is detecting the hybridization process with high precision in a real-life biological environment. Towards this end, we have studied the hybridization of single stranded (ss)-DNA anchored on a gold surface using the increase in height of the molecules upon hybridization with a label free target which is due to the much larger rigidity of ds- vs. ss-DNA. Nano-scale ss-DNA patches are assembled within oligo-ethylene-glycol terminated alkylthiol self-assembled monolayer on a gold substrate using nanografting (an atomic force microscopy-based nanolithography technique). Differential height measurements indicate that ss-DNA nano-patches do not show significant increase in height upon hybridization with complementary strands in high density regime. Moreover, the advantage of this system for biosensors and genomics applications will be discussed briefly in the end.

Biomaterials are defined as materials that are used in medical devices or are in contact with biological systems. Their application can range from skeletal systems (bone implants, knee joints, dental implants etc), cardiovascular systems (stents, catheter, heart valve etc), organs (artificial kidney, heart lung machine, skin etc) and senses (contact lens, corneal bandage etc). The field of biomaterials uses ideas from medicine, biology, physics, chemistry, materials sciences, engineering, ethics, law and health care. Biomaterials are usually integrated into devices or implants hence the interdisciplinary aspect is important for progress. The field brings together researchers from diverse academic backgrounds. They must communicate clearly. Some disciplines that intersect in the development, study and application of biomaterials include: bioengineer, chemist, chemical engineer, electrical engineer, mechanical engineer, materials scientist, biologist, microbiologist, physician, veterinarian, ethicist, nurse, lawyer, regulatory specialist and venture capitalist. Biomaterials can be metals, ceramics, polymers, glasses, carbons, and composite materials. Such materials are used as molded or machined parts, coatings, fibers, films, foams and fabrics. One of the major applications of biomaterials is in the field of tissue engineering. This field combines the knowledge of engineering, life sciences and clinical practice to solve the problem of tissue loss or damage, aimed at facilitating the regeneration of damaged or diseased tissue. The essence of tissue engineering is the use of living cells, together with degradable scaffolds and growth factors in development of implantable parts or devices for the restoration of body function. A major component in the revolutionary field of tissue engineering is the development of the suitable scaffold for seeding cells, growth factors and subsequent growth of tissues. There has been a considerable effort devoted to improving material and biological properties of scaffolds used in bone tissue engineering during the past decade. We developed and investigated different porous scaffolds with improved material properties and biological functions. An introduction to various scaffold materials developed in the lab along with future challenges will be presented towards the end.

The Asian Tiger mosquito is generally associated with the spread of dengue fever; biting around the ankles and knees close to the ground in the daytime, rarely at night. Any source of stagnant water such as in the automobile tires, open containers, trash cans, holes in the tree trunks, broken vases, which gather rainwater, are an excellent breeding place for the tiger mosquito. The situation in Pakistan has deteriorated over the past years; solid steps are needed to bring hygiene conditions an integral part of our life styles. Vectors are breeding every where and so are the microorganisms. The entire picture is ultimately leading to the worst imaginable situation, where this year dengue, and in the years to come other dipterous related diseases will be there to welcome us. There is a dire need to make short and long term planning by including our environment as the major concerns of the future issues. Our research team, at the Department of Agro-entomology, has initiated work in this direction and we will be developing strategies to forecast the out breaks of mosquitoes and onset of disease. These steps will help in better management of mosquitoes through the development of potent plant extracts.

Studies of the DNA sequence are paving the ways to diagnose diseases at much early stages leading to possible cures of cancer. Presence of mutated genes could be considered a risk for undesired production of proteins resulting in diseases like cancer. This seminar will highlight the biology of the microarrays, different classification techniques to diagnose cancer and the necessary tools to increase the accuracy of diagnosis.

We have developed computer models for the control of the activation of the calcium dependent transcription factors. Upon stimulation by foreign proteins, T-lymphocytes display spontaneous oscillation in calcium cellular concentration. Depending on the frequency of these oscillations, either one or more transcription factors are activated. The active transcription factors translocate to the nucleus and initiate gene expression. The model suggests a mechanism by which this differential gene expression occurs. This model faithfully reproduces a wide variety of experimental data. It also suggests key control points for these biochemical signalling pathways, which might suggest novel targets for immunosepressant drugs.

Biotechnology has affected different aspects of medicine in diverse ways from prevention to treatment. Great progress in new fields of medicine today, is due to recent developments in molecular biotechnology. Recombinant DNA technology or Genetic Engineering as basic tools of molecular biology has revolutionized medical science. The use of biotechnology in medicine is growing rapidly and is opening opportunities to develop new, more effective drugs and other therapeutics. Studying the genetics of humans is allowing us to understand what happens when genes go wrong in inherited diseases and to start to develop new therapies that treat the genetic cause, not the symptoms. By studying the genetic make-up of viruses, bacteria, or fungi, we can understand how they cause disease and develop better drugs and antibiotics that target them more specifically. These biotechnological approaches will be explored in different areas of medicine including prevention, pathology, diagnosis and treatment of the diseases during this talk.

The merger of life-science and engineering, specially at the micro and nanoscale, can bring about some very exciting and practical possibilities for the development of "integrated systems". Micro and nanoscale engineering can be used to solve important problems in life-sciences such as detection of biological organisms, while concepts from life sciences such as bio-inspired assembly can be used to meet significant engine manufacturing. Future integrated systems will utilize nano-scale phenomena,and micro-scale components used to interface the nano-scale components to the macro-world. This talk will present the interdisciplinary work in progress in our group in the development of these integrated systems, for example; detection of microorganisms and the determination of their viability within micro-scale bio-chips and bio-reactors, fabrication of ultra thin silicon cantilevers for high sensitivity detection of molecular byproducts of cells, integrated silicon nano-wire chemical sensors, and exploration of DNA and protein based assembly of micro and nano-particles and silicon devices.

Genome - the complete set of genetic information - determines the nature, form and activities of a living organism. Human genome, present in 23 pairs of chromosomes, consists of 3.2 billion pairs of A,T,C & G repeated over and over again in varying order. Announcement of double helical structure of DNA in 1953, cloning of first gene in 1973 and completion of the human genome sequence in June 2000 are the most outstanding landmarks of all life sciences. A race between the Human Genome Project (HGP), a publicaly funded consortium, and Celera Genomics, a private company, led to completion of human genome sequence much earlier than initially planned. Celera Genomics using a so-called shot gun sequencing strategy coupled with high speed computers using novel software went ahead of the HGP. In spite of the entire sequence known, the complete understanding of chemical structure of all the genes and how they work are decades away. Computer analysis shall be instrumental in locating all the genes within the 23 chromosomes in the human genome, which may turn out to be first step in solving all the mysteries. It will be possible to detect the genetic disorders at an early stage and to design gene therapy procedures accordingly. Pharmaceutical companies are working to create drugs tailored to a patient's genetic profile, boosting effectiveness and drastically reducing side-effects. Current developments have led to new social, philosophical and ethical issues which shall need to be tackled wisely.