This blog is part autobiography part roadmap.
I am often asked “Do you miss it-being a scientist”
The short
answer is “I didn’t dream of being an IT consultant.”
Longer answer
is, as with all things that are part of being an adult, more complicated.
- I miss discovery- the joy designing a method to answer a question and then actually knowing- for a brief moment in time- something that no one else knows.
- I miss immersing myself in a problem and building a solution.
- I don’t miss, university politics; having to know who’s ass to kiss and watching my back for potential theft of ideas.
- I don’t miss the bullshit publication process that sometimes is used for competitive reasons.
- I don’t miss trying to write a grant that appears to be both novel and safe at the same time.
- I don’t miss the bureaucracy of universities policies that protect senior faculty but burden junior faculty.
I have been
“out of the game” for half a decade now but I still pay attention to science
and design experiments in my head and sometimes write them down.
I was an
Assistant Professor running a small lab for about 4 years, my lab was centered
on a set of enzymes that control the expression of genes in response to cell
signals and environmental stimuli. These enzymes are commonly known as
epigenetic regulators. The work we did was pretty good given the lack of
funding, the fact that the enzymes had been described literally a year before I
started my lab and I was trying to combine a novel class of genes with a novel
set of methods (I was part of one of the groups that published the early papers
describing the histone demethylase enzymes).[Synopsis of my lab]
My real
interest, however has always been in learning the answer to the fundamental
question “How do you make a brain?”
I think now, I
would ask a slightly different question; which has “how do we fix the brain
when it isn’t made right.” One thing that age and distance has given me is
perspective or perhaps empathy I don’t honestly know the difference. I have two
small children both of whom are pretty awesome- unfortunately both have
inherited some of my flaws. So I am often struck by how does the brain manifest
these “flaws” even if there are no major changes or developmental issues.
How would one go after such questions?
Five years ago
the answer was Stem Cells with maybe some mouse genetics thrown in for good
measure. Now? I would go another direction. I think the single biggest issue in
epigenetic research as well as neuroscience is the lack correlation data
between phenotype (what it looks like in the whole organism), genotype (what
genes play a role) and biochemical output (how well does the “engine”
function”). Much like astrophysics and quantum physics have mathematic models
which provide probability maps for specific core particles and/or forces,
Epigenetics needs probability maps for phenotype and genotype- a Heisenberg
probability if you will.
As I have
mentioned in other posts, epigenetics is essentially grammar for the genome. It
is a big, unwieldy mess of a field that is likely at least three separate full
fields that we do not have names for as of yet. Sticking with the analogy the
“field” of epigenetics is at the point where Western civilization was in the
late 1700s/early 1800s where we knew some words and potentially some word
relationships in the Egyptian cuneiform but we were largely blind to what was
actually being said in hieroglyphs until the Rosetta stone
was found. To me the rosetta stone for epigenetics will be cross species
mapping of real world consequences.
For example; we know that there is a link between obesity in dogs and
their owners. That is a
real world cross species phenotype- why don’t we look at what genes expression
and epigenetic patterns are changed as both lose weight? There is still
validity to the idea mammalian biology is conserved at the physiological level.
What I would do
if I was starting now would be to focus on dogs as a main model; they live with
us, they often eat like us, they have behaviours which at their core are
similar enough to ours but distinct across breeds. Furthermore access to their
health records would have less risk and potentially greater detail as most
veterinarians have a depth of knowledge on their patients over a whole lifetime
– and for some clients multiple dog lifetimes.
For me, I would
focus on brain cancer- as a scientist it is a fascinating process to take a
cell that is programmed to not multiply and make it multiply and it is a cancer
type that has repercussions to ones body, dignity and family.
The lab would
have five facets;
1.
Define
a set of neurologic symptoms that could be tested for by a veterinarian in
clinic.
a.
Use
standard indications from observation.
b.
A
set of typical blood markers that are used for “unhealthy’ as part of the
analysis.
c.
X-rays
to define rough location, size and prognosis
2.
Test
brain tumour samples across gene expression, “Epigenetic profile”, potentially
genome mutations
3.
Use
samples to grow models tumours, testing their gene expression profile and
epigenetics profile for changes in culture.
a.
Where
possible have normal age specific controls across breeds (or at least a general
“mutt” control)
4.
Longitudinal
studies of dogs with tumors after various therapies.
5.
Map
epigenetic changes in tumour versus normal as well as fresh tumour versus in
culture.
I was
“classically” trained as a mouse geneticist where we had the clean clear; I
deleted a gene what happened to my cell type? I learned [the very hard
way- hello consulting ;{ ] that there
are no one-to-one relationships in any cell type when we deal with epigenetics-
it is the system that protects the cell from single points of failure.
