Hypothesis-1: Aid in cancer research

There is a significant increase in occurrence of cancer around the world. This isn’t to say
that there is no progress made towards treatment of cancer. Survival rates have almost been
doubled in the last 40 years due to the ever-going research in this field. But alongside the
undeniable improvements in care, it should be noted that the scale of the problem has
increased. Previously it was predicted that 1 in 3 would develop cancer at some point in their
life, but for some reason, despite the increasing progress in the field of cancer research the
current studies have updated the prediction, now stating 1 in 2 are likely to encounter cancer at
some point in their lives.
The best way to cure cancer is to prevent it, or at least detect it in the early stages if
possible. There has been a lot of progress in early detection, but one of the biggest challenges
that still remains unsolved is mapping mutated genes to the victim organ or tissue that starts to
develop a tumor.
Aim: The aim is to understand why does mutation in genes cause cancer only in certain
parts of the body. For example, let’s say there is a mutation occurring in the genome, due to
which breast cancer is developed. Our aim is to understand why such a mutation caused breast
cancer, and not lung cancer or any other cancer. The aim of the research is to establish
relationship between mutated gene and tissue specificity for cancer.
Abstract: Studies related to mapping of genes to tissues affected are already under
progress, but in our study we are more focused on why a particular tissue is affected, ie our
focus is not just to figure out change in ‘gene x’ causes breast cancer, but also to find out why
such a change in ‘gene x’ caused only breast cancer and not any other cancer. For this we
propose a theoretical model based on Lab-On-Chip technology.
The LOC models that exist so far concentrate on protein crystallization, DNA, or specific
organs like lung-on-a-chip, liver-on-a-chip etc. The existing models either focus on the genomic
level entirely, or on the tissue level. In our model, we are trying alter gene sequences of
different kinds of cells present in microchips, that were previously growing as healthy cells in
vivo. We do not need to have a really complex human like arrangement on a chip in order to
establish relationship between gene and tissue specific tumor.
Our model chip:
1) Will contain different kind of tissues cultured in microscale at different locations
mimicking the human tissue arrangement.
2) Will include mechanisms that can provide alterations in gene sequences of the cells
proliferating in the microchannels.
Working: We could have a microfluidic based chip ready with cells that express only a
certain part of the complete genome. For example, let’s consider breast cancer. We will only
alter the gene responsible for breast cancer. The genes responsible for breast cancer have
already been identified. The cells happen to have expressed the gene that ends up getting
altered. Since we are emulating the human tissues, there will be significant tumor development
noticed in the breast cell culture. We now use cells from other parts of the body to grow a
three-dimensional based model mimicking corresponding organs from which they were
derived. Careful subjection to the same kind of alteration mechanisms would mean the genes
getting altered would be the same in all types of cell, factor lies if the cells in question express
that gene or not. In order to understand the tissue specificity of the gene mutation, we will
have to consider a lot of possible parameters like the kind of proteins produced in each tissue,
the changes in intercellular signaling etc. These parameters are detectable by making the chip
real time monitored. By varying one parameter keeping other parameters the same and
studying the different changes in each tissue, it might be possible to develop a prediction
model, which can be used to predict where in the human body a tumor will be developed as a
result of a certain mutation.
In a case where a defective gene sequence leading to breast cancer fails to produce in-
human like result on the chip, it is highly possible that apart from the mutated genes, there are
also other genes that aren’t mutated that play an important role in tumor development. The
impact of other genes on the faulty gene mutation can be similar to epistasis interaction, or
another interaction which will require in depth research on the topic. In any case, such a model
will provide a lot of scope for further studies related to tissue specific nature of cancer. This will
also open up new possibilities for tissue specific cancer drug testing in the presence of various
kinds of tissues.
The experiment would involve identifying patterns (relating gene mutation and callus
production), analyzing the patterns using bioinformatics tools (for example in relating mutation
in gene to concentration of proteins produced) and various other techniques that help in gene
identification, comparison etc.
The hypotheses mainly involve the following:
1) Microfabrication as base for construction of chip
2) Culturing of different kinds of tissues at low volumes on the microchip using
microfluidics
3) Bioinformatics and statistical analysis to draw inferences
Apart from these there is also requirement of techniques for gene isolation, amplification etc.
This is however only a theoretical model that has a lot of scope to improve on. In order
to further understand the challenges, practicality, feasibility and impact of this theoretical
model, we will require further assistance from experts in the respective fields.