The Effect of Stiffness on Mechanotransduction and Metabolism in Multiple Sclerosis

Allyson Henry Author

04/05/2021 Added

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UCARE engineering, Glycolysis and Mechanotransdution as it relates to Multiple Sclerosis

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[00:00:01.890]Hello everyone, my name is Allyson Henry.
[00:00:04.440]Thank you for watching my presentation today.
[00:00:07.470]My project is titled, "The Effect of Stiffness
[00:00:10.130]on Mechanotransduction and Metabolism
[00:00:12.500]in Multiple Sclerosis".
[00:00:15.690]So first I'm just gonna tell you
[00:00:17.128]about what multiple sclerosis is.
[00:00:20.470]It's a disease that affects the ways
[00:00:22.470]in which people speak, see, feel and think.
[00:00:25.540]Some of its symptoms include loss of vision,
[00:00:28.420]bladder and bowel problems, unusual nerve pain and fatigue.
[00:00:32.890]And people with this disease lack the capacity
[00:00:35.870]to properly repair myelin in their brain.
[00:00:38.920]There are four types of multiple sclerosis
[00:00:41.070]including progressive relapsing remitting,
[00:00:43.370]relapsing-remitting, secondary-progressive
[00:00:46.100]and primary progressive.
[00:00:47.810]And it is an auto-immune disorder that affects
[00:00:50.840]around 2.5 out of every 1,000 people.
[00:00:54.500]Currently, there are drugs available to help treat MS
[00:00:57.980]but there is no cure
[00:00:59.290]and so it's important to study multiple sclerosis
[00:01:02.090]so we can learn more about its pathology
[00:01:04.420]and hopefully develop better drugs or eventually cure it.
[00:01:09.610]Who does multiple sclerosis affect?
[00:01:11.800]It affects more women than men
[00:01:13.590]although it is unknown why this occurs.
[00:01:17.430]It is commonly diagnosed between 20 to 40 years of age.
[00:01:20.840]And it is one of the most common neurodegenerative diseases
[00:01:24.390]found in young adults.
[00:01:28.760]So for my project, I'm looking into mechanotransduction
[00:01:31.897]and metabolism as it relates to multiple sclerosis.
[00:01:36.100]So some of the mechanotransduction pathways
[00:01:39.010]or categories of interests that I'll be looking into
[00:01:41.511]are the YAP/TAZ pathway, glioma invasion or angiogenesis,
[00:01:46.870]the FAK pathway, Rho GTPases, RTKs and the ERK pathway.
[00:01:53.740]For metabolism, I'm looking into glycolysis,
[00:01:57.150]the PPP pathway, the TCA cycle and Oxphos.
[00:02:06.160]So to begin my projects,
[00:02:09.010]I'm looking to find target genes related
[00:02:12.010]to metabolism and mechanotransduction
[00:02:15.400]that appear to be dysregulated in multiple sclerosis.
[00:02:19.595]And to do this, I've been looking into databases,
[00:02:23.710]taking from multiple sclerosis patients to see
[00:02:29.120]what genes are being dysregulated in patients
[00:02:32.190]with multiple sclerosis.
[00:02:34.600]The table shown on this slide shows some of the statistics
[00:02:37.869]from the databases I've been using.
[00:02:41.100]So for my first database as you can see,
[00:02:44.290]there were 10 healthy patient samples
[00:02:47.155]and 14 multiple sclerosis patient samples.
[00:02:51.370]From my second database,
[00:02:52.700]there were eight healthy patient samples
[00:02:54.480]and eight multiple sclerosis patient samples
[00:02:57.330]and for my third database, I had 15 healthy patient samples
[00:03:01.180]and 14 multiple sclerosis patient samples.
[00:03:05.650]And then one other thing that I wanted to note
[00:03:08.230]is that two of these databases
[00:03:12.300]contains more woman patient samples than men.
[00:03:16.370]And this is most likely due to the fact that more women
[00:03:22.640]are diagnosed with multiple sclerosis than men.
[00:03:30.570]So when I look into mechanotransduction,
[00:03:35.410]this slide just shows the genes of interest
[00:03:37.670]that I was looking at
[00:03:39.110]along with their respective pathways or categories.
[00:03:43.690]And after searching through the databases and pulling out
[00:03:48.480]all the individual data from these gene expressions,
[00:03:52.660]significance tests were performed on the databases
[00:03:55.780]to determine if a regulation in the genes was significant.
[00:04:06.670]So for my first database, I found all of these genes
[00:04:12.190]at the bottom to be significant and the graphs at the top
[00:04:16.440]show how I determined if they were significant.
[00:04:21.570]So I used a program called Prism to create these graphs
[00:04:27.100]and on the y-axis as you can see,
[00:04:29.640]it shows the gene expression
[00:04:31.670]and then on the x-axis we have the normal
[00:04:34.680]versus the disease patient samples
[00:04:38.450]and the dots represent all of the individual data points.
[00:04:44.510]And then at the top, the bar at the top of the star
[00:04:47.930]shows the level of significance of the genes.
[00:04:56.310]So I performed the same thing for my second database
[00:04:59.430]as you can see,
[00:05:01.630]there are some of those examples of this
[00:05:04.330]the statistical analysis at the top and then the genes
[00:05:09.480]at the bottom are the ones
[00:05:11.620]that I found to be statistically significant.
[00:05:15.690]For my third dataset regarding mechanotransduction,
[00:05:19.860]none of the genes appeared to be statistically significant.
[00:05:23.820]But this could be due to the small sample size.
[00:05:27.080]I'll remind you, there were eight healthy patient samples
[00:05:30.340]and eight multiple sclerosis patient samples.
[00:05:36.320]Next, I looked into metabolism genes
[00:05:38.880]to see the dysregulation in these,
[00:05:42.610]below just shows the genes of interest
[00:05:45.330]and their respective pathways again for metabolism.
[00:05:50.530]So I performed this just statistical tests again,
[00:05:54.150]with the metabolism genes this time.
[00:05:56.780]And as you can see
[00:05:58.173]those are just some examples of the graphs again.
[00:06:01.220]I didn't put them all on here for the sake of
[00:06:05.290]they took up a lot of room on the slide.
[00:06:08.230]And then at the bottom
[00:06:09.869]those are all this statistically significant genes
[00:06:13.470]that I found from that database.
[00:06:18.590]I performed the same thing for the second database.
[00:06:25.170]And then for the third database,
[00:06:26.740]I only found two statistically significant genes.
[00:06:34.400]So overall I found 18 mechanotransduction genes
[00:06:38.790]to be statistically significant.
[00:06:41.080]From my first database, 16 to be significant
[00:06:44.550]for my second database
[00:06:46.010]and none to be significant from my third database.
[00:06:49.570]And for metabolism I found 15 genes
[00:06:52.610]to be statistically significant for my first database,
[00:06:55.740]seven to be significant for my second database
[00:06:58.960]and two to be significant from my third database.
[00:07:04.850]The future directions of my project include determining
[00:07:09.270]which genes I want to target for my next step.
[00:07:13.520]Currently, I'm waiting on permission
[00:07:15.700]to gain access to more databases.
[00:07:18.810]They're kind of limited in the databases
[00:07:21.490]that are accessible for the general public
[00:07:24.510]and I just want some more databases to look at
[00:07:28.370]because we're trying to create a strong argument
[00:07:30.770]for our genes of interests and why we chose our target genes
[00:07:34.744]and more data to draw conclusions from is preferred.
[00:07:39.470]And then the next step in my project
[00:07:41.400]will be to see microglia
[00:07:43.100]which are glial cells involved in multiple sclerosis
[00:07:46.550]onto plates with differing stiffnesses
[00:07:49.120]to determine if stiffness plays a role
[00:07:51.400]in the pathology of multiple sclerosis.
[00:07:54.560]And the reason we're doing this is because
[00:07:56.510]other studies have shown that brain plasticity decreases
[00:08:00.140]with the progression of multiple sclerosis.
[00:08:02.720]So we wanna see if this decreasing elasticity
[00:08:07.100]is actually causing a positive feedback loop
[00:08:11.020]in driving the progression of multiple sclerosis as well.
[00:08:17.810]And then I just want to acknowledge Dr. Srivatsan Kidambi
[00:08:22.240]and the Focus Lab members
[00:08:24.350]because they've all been so helpful
[00:08:26.120]in helping me start getting into research
[00:08:30.730]and thank you for watching my presentation today.

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The Effect of Stiffness on Mechanotransduction and Metabolism in Multiple Sclerosis

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